]> Dumontier Lab application/rdf+xml Michel Dumontier Enzyme Commission Ontology (primitive) Biochemical reactions as defined by the enzyme commission. 2007-10-01 en 1.0 Oxidoreductases Acting on the CH-OH group of donors With NAD(+) or NADP(+) as acceptor Aldehyde reductase Alcohol dehydrogenase The animal, but not the yeast, enzyme acts also on cyclic secondary alcohols. Acts on primary or secondary alcohols or hemiacetals. Zinc or iron An alcohol + NAD(+) = an aldehyde or ketone + NADH. L-xylulose reductase http://purl.uniprot.org/mim/260800 Xylitol + NADP(+) = L-xylulose + NADPH. 3-oxoacyl-[acyl-carrier-protein] reductase Exhibits a marked preference for [acyl-carrier-protein] derivatives over CoA derivatives as substrates. (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP(+) = 3-oxoacyl-[acyl-carrier-protein] + NADPH. Palmitoyldihydroxyacetone-phosphate reductase Acylglycerone-phosphate reductase Also acts on alkylglycerone 3-phosphate and alkylglycerol 3-phosphate. 1-palmitoylglycerol 3-phosphate + NADP(+) = palmitoylglycerone phosphate + NADPH. 3-dehydrosphinganine reductase KTS reductase 3-oxosphinganine reductase D-3-oxosphinganine reductase 3-ketosphinganine reductase 3-oxosphinganine:NADPH oxidoreductase D-3-oxosphinganine:B-NADPH oxidoreductase D-3-dehydrosphinganine reductase DSR Sphinganine + NADP(+) = 3-dehydrosphinganine + NADPH. L-threonine 3-dehydrogenase L-threonine + NAD(+) = L-2-amino-3-oxobutanoate + NADH. The product spontaneously decarboxylates to aminoacetone. Hydroxyproline oxidase 4-oxoproline reductase http://purl.uniprot.org/mim/237000 4-hydroxy-L-proline + NAD(+) = 4-oxoproline + NADH. Retinol dehydrogenase http://purl.uniprot.org/mim/136800 Retinol + NAD(+) = retinal + NADH. Panthothenase Pantoate 4-dehydrogenase (R)-pantoate + NAD(+) = (R)-4-dehydropantoate + NADH. Pyridoxal 4-dehydrogenase Pyridoxal + NAD(+) = 4-pyridoxolactone + NADH. The enzyme acts on the hemiacetal form of the substrate. Carnitine 3-dehydrogenase Carnitine + NAD(+) = 3-dehydrocarnitine + NADH. D-arabinitol 4-dehydrogenase D-arabinitol + NAD(+) = D-xylulose + NADH. Indolelactate dehydrogenase Indole-3-lactate dehydrogenase (Indol-3-yl)lactate + NAD(+) = (indol-3-yl)pyruvate + NADH. 3-(imidazol-5-yl)lactate dehydrogenase (S)-3-(imidazol-5-yl)lactate + NAD(P)(+) = 3-(imidazol-5-yl)pyruvate + NAD(P)H. Indanol dehydrogenase Indan-1-ol + NAD(P)(+) = indanone + NAD(P)H. 3(20)-alpha-hydroxysteroids are also oxidized, more slowly. L-xylose 1-dehydrogenase Also oxidizes D-arabinose and D-lyxose. L-xylose + NADP(+) = L-xylono-1,4-lactone + NADPH. Apiose 1-reductase D-apiose reductase D-apiitol reductase D-apiitol + NAD(+) = D-apiose + NADH. NADP-pentose-dehydrogenase Ribose 1-dehydrogenase (NADP(+)) Also acts, more slowly, on D-xylose and other pentoses. D-ribose + NADP(+) + H(2)O = D-ribonate + NADPH. D-arabinose 1-dehydrogenase D-arabinose + NAD(+) = D-arabinono-1,4-lactone + NADH. D-arabinose 1-dehydrogenase (NAD(P)(+)) D-arabinose + NAD(P)(+) = D-arabinono-1,4-lactone + NAD(P)H. Also acts on L-galactose, 6-deoxy-and 3,6-dideoxy-L-galactose. Glucose 1-dehydrogenase (NAD(+)) D-glucose + NAD(+) = D-glucono-1,5-lactone + NADH. Glucose 1-dehydrogenase (NADP(+)) Also oxidizes D-mannose, 2-deoxy-D-glucose and 2-amino-2-deoxy-D-mannose. D-glucose + NADP(+) = D-glucono-1,5-lactone + NADPH. L-arabinitol 4-dehydrogenase L-arabinitol + NAD(+) = L-xylulose + NADH. Galactose 1-dehydrogenase (NADP(+)) D-galactose + NADP(+) = D-galactonolactone + NADPH. Also acts on L-arabinose, 6-deoxy-and 2-deoxy-D-galactose. Aldose 1-dehydrogenase D-aldose + NAD(+) = D-aldonolactone + NADH. Acts on D-glucose, 2-deoxy-and 6-deoxy-D-glucose, D-galactose, 6-deoxy-D-galactose, 2-deoxy-L-arabinose and D-xylose. (2S,3R)-aldose dehydrogenase D-threo-aldose 1-dehydrogenase L-fucose dehydrogenase The animal enzyme was also shown to act on L-arabinose, and the enzyme from Pseudomonas caryophylli on L-glucose. Acts on L-fucose, D-arabinose and L-xylose. A D-threo-aldose + NAD(+) = a D-threo-aldono-1,5-lactone + NADH. Sorbose 5-dehydrogenase (NADP(+)) 5-ketofructose reductase L-sorbose + NADP(+) = 5-dehydro-D-fructose + NADPH. 5-ketofructose reductase (NADP+) 5-ketofructose reductase (NADP(+)) Fructose 5-dehydrogenase (NADP(+)) D-fructose + NADP(+) = 5-dehydro-D-fructose + NADPH. 2-keto-3-deoxygluconate oxidoreductase 2-deoxy-D-gluconate 3-dehydrogenase 2-deoxy-D-gluconate + NAD(+) = 3-dehydro-2-deoxy-D-gluconate + NADH. 2-keto-3-deoxy-D-gluconate dehydrogenase 2-dehydro-3-deoxy-D-gluconate 6-dehydrogenase 2-dehydro-3-deoxy-D-gluconate + NADP(+) = (4S,5S)-4,5-dihydroxy-2,6-dioxohexanoate + NADPH. 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase 2-keto-3-deoxygluconate dehydrogenase 2-dehydro-3-deoxy-D-gluconate + NAD(+) = (4S)-4,6-dihydroxy-2,5-dioxohexanoate + NADH. The enzyme from Pseudomonas acts equally well on NAD(+) or NADP(+), while those from Erwinia chrysanthemi and Escherichia coli are more specific for NAD(+). 5-ketogluconate 2-reductase L-idonate 2-dehydrogenase L-idonate + NADP(+) = 5-dehydro-D-gluconate + NADPH. L-threonic acid dehydrogenase L-threonate 3-dehydrogenase L-threonate + NAD(+) = 3-dehydro-L-threonate + NADH. L-arabinitol 2-dehydrogenase L-arabinitol 2-dehydrogenase (ribulose forming) L-arabinitol + NAD(+) = L-ribulose + NADH. 3-keto-L-gulonate dehydrogenase 3-dehydro-L-gulonate 2-dehydrogenase 2,3-diketo-L-gulonate reductase 3-dehydro-L-gulonate + NAD(P)(+) = (4R,5S)-4,5,6-trihydroxy-2,3-dioxohexanoate + NAD(P)H. Mannonate dehydrogenase Mannuronate reductase D-mannonate + NAD(P)(+) = D-mannuronate + NAD(P)H. GDP-mannose 6-dehydrogenase GDP-D-mannose + 2 NAD(+) + H(2)O = GDP-D-mannuronate + 2 NADH. Also uses the corresponding deoxynucleoside diphosphate derivative as a substrate. dTDP-4-keto-L-rhamnose reductase dTDP-4-dehydrorhamnose reductase dTDP-6-deoxy-L-mannose dehydrogenase In the reverse direction, reduction on the 4-position of the hexose moiety takes place only while the substrate is bound to another enzyme that catalyzes epimerization at C-3 and C-5; the complex has been referred to as dTDP-L-rhamnose synthase. dTDP-6-deoxy-L-mannose + NADP(+) = dTDP-4-dehydro-6-deoxy-L-mannose + NADPH. dTDP-6-deoxy-L-talose 4-dehydrogenase Oxidation on the 4-position of the hexose moiety takes place only while the substrate is bound to another enzyme that catalyzes epimerization at C-3 and C-5. dTDP-6-deoxy-L-talose + NADP(+) = dTDP-4-dehydro-6-deoxy-L-mannose + NADPH. GDP-6-deoxy-D-talose 4-dehydrogenase GDP-6-deoxy-D-talose + NAD(P)(+) = GDP-4-dehydro-6-deoxy-D-mannose + NAD(P)H. UDP-N-acetylglucosamine 6-dehydrogenase UDP-N-acetyl-D-glucosamine + 2 NAD(+) + H(2)O = UDP-N-acetyl-2-amino-2-deoxy-D-glucuronate + 2 NADH. Ribitol-5-phosphate 2-dehydrogenase D-ribitol 5-phosphate + NAD(P)(+) = D-ribulose 5-phosphate + NAD(P)H. NADP-dependent mannitol dehydrogenase Mannitol 2-dehydrogenase (NADP(+)) D-mannitol + NADP(+) = D-fructose + NADPH. Polyol dehydrogenase Glucitol dehydrogenase L-iditol 2-dehydrogenase Sorbitol dehydrogenase L-iditol + NAD(+) = L-sorbose + NADH. Also acts on D-glucitol (giving D-fructose) and other closely related sugar alcohols. http://purl.uniprot.org/mim/182500 Ketosephosphate reductase Glucitol-6-phosphate dehydrogenase Sorbitol-6-phosphate 2-dehydrogenase D-sorbitol 6-phosphate + NAD(+) = D-fructose 6-phosphate + NADH. 15-hydroxyprostaglandin dehydrogenase (NAD(+)) Acts on prostaglandins E(2), F(2-alpha) and B(1), but not on prostaglandin D(2) (cf. EC 1.1.1.196 and EC 1.1.1.197). (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-13-enoate + NAD(+) = (5Z,13E)-11-alpha-hydroxy-9,15-dioxoprost-13-enoate + NADH. D-pinitol dehydrogenase 1D-3-O-methyl-chiro-inositol + NADP(+) = 2D-5-O-methyl-2,3,5/4,6-pentahydroxycyclohexanone + NADPH. Sequoyitol dehydrogenase 5-O-methyl-myo-inositol + NAD(+) = 2D-5-O-methyl-2,3,5/4,6-pentahydroxycyclohexanone + NADH. Perillyl-alcohol dehydrogenase Oxidizes a number of primary alcohols with the alcohol group allylic to an endocyclic double bond and a 6-membered ring, either aromatic or hydroaromatic. Perillyl alcohol + NAD(+) = perillyl aldehyde + NADH. 3-beta-hydroxy-5-ene steroid dehydrogenase Progesterone reductase 3-beta-hydroxy-Delta(5)-steroid dehydrogenase Acts on 3-beta-hydroxyandrost-5-en-17-one to form androst-4-ene-3,17-dione and on 3-beta-hydroxypregn-5-en-20-one to form progesterone. http://purl.uniprot.org/mim/201810 A 3-beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-steroid + NADH. 11-beta-hydroxysteroid dehydrogenase Corticosteroid 11-beta-dehydrogenase http://purl.uniprot.org/mim/207765 http://purl.uniprot.org/mim/604931 http://purl.uniprot.org/mim/218030 An 11-beta-hydroxysteroid + NADP(+) = an 11-oxosteroid + NADPH. 16-alpha-hydroxysteroid dehydrogenase A 16-alpha-hydroxysteroid + NAD(P)(+) = a 16-oxosteroid + NAD(P)H. Estradiol 17-alpha-dehydrogenase Estradiol-17-alpha + NAD(P)(+) = estrone + NAD(P)H. 20-alpha-hydroxysteroid dehydrogenase A-specific with respect to NAD(P)(+) (cf. EC 1.1.1.62). 17-alpha,20-alpha-dihydroxypregn-4-en-3-one + NAD(P)(+) = 17-alpha-hydroxyprogesterone + NAD(P)H. D-iditol 2-dehydrogenase D-iditol + NAD(+) = D-sorbose + NADH. Also converts xylitol into L-xylulose and L-glucitol into L-fructose. 21-hydroxysteroid dehydrogenase (NAD(+)) Pregnan-21-ol + NAD(+) = pregnan-21-al + NADH. Acts on a number of 21-hydroxycorticosteroids. 21-hydroxysteroid dehydrogenase (NADP(+)) NADP-21-hydroxysteroid dehydrogenase 21-hydroxy steroid dehydrogenase (nicotinamide adenine dinucleotide phosphate) 21-hydroxy steroid (nicotinamide adenine dinucleotide phosphate) dehydrogenase 21-hydroxy steroid dehydrogenase Acts on a number of 21-hydroxycorticosteroids. Pregnan-21-ol + NADP(+) = pregnan-21-al + NADPH. 3-alpha-hydroxy-5-beta-androstane-17-one 3-alpha-dehydrogenase Etiocholanolone 3-alpha-dehydrogenase 3-alpha-hydroxy-5-beta-androstane-17-one + NAD(+) = 5-beta-androstane-3,17-dione + NADH. Sepiapterin reductase 7,8-dihydrobiopterin + NADP(+) = sepiapterin + NADPH. http://purl.uniprot.org/mim/182125 Ureidoglycolate dehydrogenase (S)-ureidoglycolate + NAD(P)(+) = oxalureate + NAD(P)H. Glycerol 2-dehydrogenase (NADP(+)) Dihydroxyacetone reductase Glycerol + NADP(+) = glycerone + NADPH. 3-hydroxybutyryl-CoA dehydrogenase BHBD Beta-hydroxybutyryl-CoA dehydrogenase (S)-3-hydroxybutanoyl-CoA + NADP(+) = 3-acetoacetyl-CoA + NADPH. UDP-N-acetylmuramate dehydrogenase UDP-N-acetylglucosamine-enoylpyruvate reductase UDP-N-acetylenolpyruvoylglucosamine reductase Uridine diphospho-N-acetylglucosamine-enolpyruvate reductase UDP-GlcNAc-enoylpyruvate reductase Uridine diphosphoacetylpyruvoylglucosamine reductase Uridine-5'-diphospho-N-acetyl-2-amino-2-deoxy-3-O-lactylglucose:NADP-oxidoreductase FAD UDP-N-acetylmuramate + NADP(+) = UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine + NADPH. Sodium dithionite, sodium borohydride and, to a lesser extent, NADH can replace NADPH. 7-alpha-hydroxysteroid dehydrogenase Catalyzes the oxidation of the 7-alpha-hydroxy group of bile acids and alcohols both in their free and conjugated forms. 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholanate + NAD(+) = 3-alpha,12-alpha-dihydroxy-7-oxo-5-beta-cholanate + NADH. The Bacteroides fragilis and Clostridium enzymes can also utilize NADP(+). Galactitol 2-dehydrogenase Galactitol + NAD(+) = D-tagatose + NADH. Also converts other alditols containing an L-threo-configuration adjacent to a primary alcohol group into the corresponding sugars. Dihydrobunolol dehydrogenase Bunolol reductase (+-)-5-((tert-butylamino)-2'-hydroxypropoxy)-1,2,3,4-tetrahydro-1-naphthol + NADP(+) = (+-)-5-((tert-butylamino)-2'-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone + NADPH. Also acts, more slowly, with NAD(+). TEHC-NAD oxidoreductase Cholestanetetraol 26-dehydrogenase 5-beta-cholestane-3-alpha,7-alpha,12-alpha,26-tetraol + NAD(+) = 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-al + NADH. D-erythrulose reductase Erythrulose reductase Also acts, more slowly, with NAD(+). Erythritol + NADP(+) = D-erythrulose + NADPH. Cyclopentanol dehydrogenase Cyclopentanol + NAD(+) = cyclopentanone + NADH. 4-methylcyclohexanol and cyclohexanol can also act as substrates. Hexadecanol dehydrogenase The Euglena enzyme also oxidizes the corresponding aldehydes to fatty acids. Hexadecanol + NAD(+) = hexadecanal + NADH. The liver enzyme acts on long-chain alcohols from C(8) to C(16). 2-alkyn-1-ol dehydrogenase 2-butyne-1,4-diol + NAD(+) = 4-hydroxy-2-butynal + NADH. NADP(+) also acts as acceptor, but more slowly. Acts on a variety of 2-alkyn-1-ols, and also on 1,4-butanediol. Hydroxycyclohexanecarboxylate dehydrogenase Acts on hydroxycyclohexanecarboxylates that have an equatorial carboxy group at C-1, an axial hydroxy group at C-3 and an equatorial hydroxy or carbonyl group at C-4, including (-)-quinate and (-)-shikimate. (1S,3R,4S)-3,4-dihydroxycyclohexane-1-carboxylate + NAD(+) = (1S,4S)-4-hydroxy-3-oxocyclohexane-1-carboxylate + NADH. Hydroxymalonate dehydrogenase Hydroxymalonate + NAD(+) = oxomalonate + NADH. 2-dehydropantoyl-lactone reductase (A-specific) 2-ketopantoyl lactone reductase Ketopantoyl lactone reductase 2-dehydropantolactone reductase (A-specific) The enzyme from Saccharomyces cerevisiae differs from that from Escherichia coli (EC 1.1.1.214), which is specific for the B-face of NADP, and in receptor requirements from EC 1.1.99.26. (R)-pantolactone + NADP(+) = 2-dehydropantolactone + NADPH. Ketopantoate reductase 2-dehydropantoate 2-reductase Ketopantoic acid reductase KPA reductase (R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH. Mannitol-1-phosphate 5-dehydrogenase D-mannitol 1-phosphate + NAD(+) = D-fructose 6-phosphate + NADH. 3-beta-hydroxy-4-beta-methylcholestenecarboxylate 3-dehydrogenase (decarboxylating) 3-beta-hydroxy-4-beta-methylcholestenoate dehydrogenase Sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) 3-beta-hydroxy-4-alpha-methylcholestenecarboxylate 3-dehydrogenase (decarboxylating) Sterol 4-alpha-carboxylic decarboxylase Also acts on 3-beta-hydroxy-5-alpha-cholest-7-ene-4-alpha-carboxylate. 3-beta-hydroxy-4-beta-methyl-5-alpha-cholest-7-ene-4-alpha-carboxylate + NAD(P)(+) = 4-alpha-methyl-5-alpha-cholest-7-en-3-one + CO(2) + NAD(P)H. 2-ketoadipate reductase 2-oxoadipate reductase Alpha-ketoadipate reductase 2-hydroxyadipate + NAD(+) = 2-oxoadipate + NADH. L-rhamnose 1-dehydrogenase L-rhamnofuranose + NAD(+) = L-rhamno-1,4-lactone + NADH. Cyclohexane-1,2-diol dehydrogenase Also oxidizes, more slowly, the cis isomer and 2-hydroxycyclohexanone. Trans-cyclohexane-1,2-diol + NAD(+) = 2-hydroxycyclohexan-1-one + NADH. D-xylose 1-dehydrogenase NAD-D-xylose dehydrogenase NAD-linked D-xylose dehydrogenase D-xylose dehydrogenase D-xylose + NAD(+) = D-xylonolactone + NADH. 12-alpha-hydroxysteroid dehydrogenase Also acts on bile alcohols. 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholanate + NADP(+) = 3-alpha,7-alpha-dihydroxy-12-oxo-5-beta-cholanate + NADPH. Catalyzes the oxidation of the 12-alpha-hydroxy group of bile acids, both in their free and conjugated form. Glycerol-3-phosphate 1-dehydrogenase (NADP(+)) sn-glycerol 3-phosphate + NADP(+) = D-glyceraldehyde 3-phosphate + NADPH. 3-hydroxy-2-methylbutyryl-CoA dehydrogenase 2-methyl-3-hydroxybutyryl-CoA dehydrogenase Also acts, more slowly, on (2S,3S)-2-hydroxy-3-methylpentanoyl-CoA. (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methylacetoacetyl-CoA + NADH. D-xylose-NADP dehydrogenase D-xylose 1-dehydrogenase (NADP(+)) D-xylose + NADP(+) = D-xylono-1,5-lactone + NADPH. Also acts, more slowly, on L-arabinose and D-ribose. Myo-inositol 2-dehydrogenase Inositol 2-dehydrogenase Myo-inositol + NAD(+) = 2,4,6/3,5-pentahydroxycyclohexanone + NADH. 3-beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase Cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase Cholest-5-ene-3-beta,7-alpha-diol + NAD(+) = 7-alpha-hydroxycholest-4-en-3-one + NADH. Highly specific for 3-beta-hydroxy-C(27)-steroids with Delta(5)-double bond. Geraniol dehydrogenase Geraniol + NADP(+) = geranial + NADPH. Also acts, more slowly, on nerol, farnesol and citronellol. NADPH-dependent carbonyl reductase Prostaglandin 9-ketoreductase Aldehyde reductase I Carbonyl reductase (NADPH) Xenobiotic ketone reductase R-CHOH-R' + NADP(+) = R-CO-R' + NADPH. B-specific with respect to NADPH (cf. EC 1.1.1.2). Acts on a wide range of carbonyl compounds, including quinones, aromatic aldehydes, ketoaldehydes, daunorubicin, and prostaglandins E and F, reducing them to the corresponding alcohol. L-glycol dehydrogenase An L-glycol + NAD(P)(+) = a 2-hydroxycarbonyl compound + NAD(P)H. In the reverse direction, vicinal diketones, glyceraldehyde, glyoxal, methylglyoxal, 2-oxo-hydroxyketones and 2-ketoacid esters can be reduced. The 2-hydroxycarbonyl compound formed can be further oxidized to a vicinal dicarbonyl compound. dTDP-galactose 6-dehydrogenase Thymidine-diphosphate-galactose dehydrogenase dTDP-D-galactose + 2 NADP(+) + H(2)O = dTDP-D-galacturonate + 2 NADPH. GDP-4-keto-6-deoxy-D-mannose reductase GDP-4-keto-D-rhamnose reductase GDP-4-dehydro-D-rhamnose reductase Guanosine diphosphate-4-keto-D-rhamnose reductase GDP-6-deoxy-D-mannose + NAD(P)(+) = GDP-4-dehydro-6-deoxy-D-mannose + NAD(P)H. In the reverse reaction, a mixture of GDP-D-rhamnose and its C-4 epimer is formed. Prostaglandin-D(2) 11-reductase Prostaglandin-D(2) ketoreductase Prostaglandin-D(2) 11-ketoreductase PGD(2) 11-ketoreductase PGF synthetase Prostaglandin-F synthetase Prostaglandin 11-ketoreductase Prostaglandin-F synthase Reduces prostaglandin D(2) and prostaglandin H(2) to prostaglandin F(2); prostaglandin D(2) is not an intermediate in the reduction of prostaglandin H(2). Also catalyzes the reduction of a number of carbonyl compounds, such as 9,10-phenanthroquinone and 4-nitroacetophenone. (5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH. Prostaglandin-E(2) 9-reductase 9-keto-prostaglandin E(2) reductase Prostaglandin-E2 9-reductase 9-ketoprostaglandin reductase PGE(2) 9-oxoreductase Prostaglandin-E(2) 9-oxoreductase PGE(2) 9-ketoreductase (5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH. Reduces prostaglandin E(2) to prostaglandin F(2)-alpha. May be identical with EC 1.1.1.197. A number of other 9-oxo-and 15-oxo-prostaglandin derivatives can also be reduced to the corresponding hydroxy compounds. D-glucuronate reductase Glucuronate dehydrogenase D-glucuronate dehydrogenase TPN-L-gulonate dehydrogenase L-glucuronate reductase Glucuronate reductase NADP-L-gulonate dehydrogenase Aldehyde reductase II Aldehyde reductase L-gulonate + NADP(+) = D-glucuronate + NADPH. Also reduces D-galacturonate. May be identical with EC 1.1.1.2. Indoleacetaldehyde reductase Indole-3-acetaldehyde reductase (NADH) (Indol-3-yl)ethanol + NAD(+) = (indol-3-yl)acetaldehyde + NADH. Indole-3-acetaldehyde reductase (NADPH) (Indol-3-yl)ethanol + NADP(+) = (indol-3-yl)acetaldehyde + NADPH. Long-chain-alcohol dehydrogenase Fatty alcohol oxidoreductase A long-chain alcohol + 2 NAD(+) + H(2)O = a long-chain carboxylate + 2 NADH. Hexadecanol is a good substrate. 5-amino-6-(5-phosphoribosylamino)uracil reductase 5-amino-6-(5-phosphoribitylamino)uracil + NADP(+) = 5-amino-6-(5-phosphoribosylamino)uracil + NADPH. Coniferyl-alcohol dehydrogenase Coniferyl alcohol + NADP(+) = coniferyl aldehyde + NADPH. Specific for coniferyl alcohol; does not act on cinnamyl alcohol, 4-coumaryl alcohol or sinapyl alcohol. CAD Cinnamyl-alcohol dehydrogenase Acts on coniferyl alcohol, sinapyl alcohol, 4-coumaryl alcohol and cinnamyl alcohol (cf. EC 1.1.1.194). Cinnamyl alcohol + NADP(+) = cinnamaldehyde + NADPH. Prostaglandin-D 15-dehydrogenase (NADP(+)) Prostaglandin-D 15-dehydrogenase (NADP+) 15-hydroxyprostaglandin-D dehydrogenase (NADP(+)) Specific for prostaglandins D (cf. EC 1.1.1.141 and EC 1.1.1.197). (5Z,13E)-(15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADP(+) = (5Z,13E)-9-alpha-hydroxy-11,15-dioxoprosta-5,13-dienoate + NADPH. 15-hydroxyprostaglandin dehydrogenase (NADP(+)) Acts on prostaglandins E(2), F(2)-alpha and B(1), but not on prostaglandin D(2) (cf. EC 1.1.1.141 and EC 1.1.1.196). May be identical with EC 1.1.1.189. (13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-13-enoate + NADP(+) = (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-enoate + NADPH. (+)-borneol dehydrogenase (+)-borneol + NAD(+) = (+)-camphor + NADH. NADP(+) can also act, more slowly. (S)-usnate reductase In the reverse direction, (S)-usnate is reduced by NADH with cleavage of the ether bond to form a 7-hydroxy group. Aldehyde reductase (NADPH) Alcohol dehydrogenase (NADP(+)) A-specific with respect to NADPH. Zinc May be identical with EC 1.1.1.19, EC 1.1.1.33 and EC 1.1.1.55. An alcohol + NADP(+) = an aldehyde + NADPH. Some members of this group oxidize only primary alcohols; others act also on secondary alcohols. Glucuronolactone reductase L-gulono-1,4-lactone + NADP(+) = D-glucurono-3,6-lactone + NADPH. NADP-dependent D-sorbitol-6-phosphate dehydrogenase Aldose-6-phosphate reductase (NADPH) In the reverse reaction, acts also on D-galactose 6-phosphate and, more slowly, on D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate. D-sorbitol 6-phosphate + NADP(+) = D-glucose 6-phosphate + NADPH. NADP-dependent 7-beta-hydroxysteroid dehydrogenase 7-beta-hydroxysteroid dehydrogenase (NADP(+)) A 7-beta-hydroxysteroid + NADP(+) = a 7-oxosteroid + NADPH. Catalyzes the oxidation of the 7-beta-hydroxy group of bile acids such as ursodeoxycholate. 1,3-propanediol dehydrogenase 3-hydroxypropionaldehyde reductase 1,3-propanediol oxidoreductase Propane-1,3-diol + NAD(+) = 3-hydroxypropanal + NADH. Uronic acid dehydrogenase Uronate dehydrogenase Also acts on D-glucuronate. D-galacturonate + NAD(+) + H(2)O = D-galactarate + NADH. Inosinic acid dehydrogenase Inosine 5'-monophosphate dehydrogenase IMP oxidoreductase Inosine monophosphate oxidoreductase IMP dehydrogenase Inosinate dehydrogenase http://purl.uniprot.org/mim/180105 The enzyme acts on the hydroxy group of the hydrated derivative of the substrate. Inosine 5'-phosphate + NAD(+) + H(2)O = xanthosine 5'-phosphate + NADH. Tropine dehydrogenase Tropine + NADP(+) = tropinone + NADPH. Also oxidizes other tropan-3-alpha-ols, but not the corresponding beta-derivatives. Monoterpenoid dehydrogenase (-)-menthol dehydrogenase (-)-menthol + NADP(+) = (-)-menthone + NADPH. Not identical with EC 1.1.1.208. Acts on a number of other cyclohexanols and cyclohexenols. (+)-neomenthol dehydrogenase Monoterpenoid dehydrogenase Not identical with EC 1.1.1.207. (+)-neomenthol + NADP(+) = (-)-menthone + NADPH. Acts on a number of other cyclohexanols and cyclohexenols. 3(or 17)-alpha-hydroxysteroid dehydrogenase Androsterone + NAD(P)(+) = 5-alpha-androstane-3,17-dione + NAD(P)H. Acts on the 3-alpha-hydroxy group of androgens of the 5-alpha-androstane series; and also, more slowly, on the 17-alpha-hydroxyl group of both androgenic and estrogenic substrates (cf. EC 1.1.1.51). Aldose reductase Polyol dehydrogenase (NADP(+)) Aldehyde reductase Wide specificity. Alditol + NAD(P)(+) = aldose + NAD(P)H. Progesterone reductase 3-beta-HSD 3-beta-(or 20-alpha)-hydroxysteroid dehydrogenase Also acts on 20-alpha-hydroxysteroids. 5-alpha-androstan-3-beta,17-beta-diol + NADP(+) = 17-beta-hydroxy-5-alpha-androstan-3-one + NADPH. Beta-hydroxyacyl-CoA dehydrogenase Long-chain-3-hydroxyacyl-CoA dehydrogenase http://purl.uniprot.org/mim/609016 http://purl.uniprot.org/mim/609015 Acts most rapidly on derivatives with chain length C(8) or C(10) (cf. EC 1.1.1.35). (S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH. 3-oxoacyl-[acyl-carrier-protein] reductase (NADH) Forms part of the fatty acid synthase system in plants. (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NAD(+) = 3-oxoacyl-[acyl-carrier-protein] + NADH. Can be separated from EC 1.1.1.100. 3-alpha-hydroxysteroid dehydrogenase (A-specific) A-specific with respect to NAD(+) or NADP(+) (cf. EC 1.1.1.50). Also acts on other 3-alpha-hydroxysteroids. Androsterone + NAD(P)(+) = 5-alpha-androstane-3,17-dione + NAD(P)H. 2-ketopantoyl lactone reductase 2-dehydropantolactone reductase (B-specific) 2-dehydropantoyl-lactone reductase (B-specific) Ketopantoyl lactone reductase (R)-pantolactone + NADP(+) = 2-dehydropantolactone + NADPH. The Escherichia coli enzyme differs from that from Saccharomyces cerevisiae (EC 1.1.1.168), which is specific for the A-face of NADP, and in receptor requirements from EC 1.1.99.26. 2-keto-D-gluconate reductase 2-ketogluconate reductase Gluconate 2-dehydrogenase D-gluconate + NADP(+) = 2-dehydro-D-gluconate + NADPH. Also acts on L-idonate, D-galactonate and D-xylonate. Farnesol dehydrogenase 2-trans,6-trans-farnesol + NADP(+) = 2-trans,6-trans-farnesal + NADPH. Also acts, more slowly, on 2-cis,6-trans-farnesol, geraniol, citronerol and nerol. Benzyl 2-methyl-3-hydroxybutyrate dehydrogenase Benzyl-2-methyl-hydroxybutyrate dehydrogenase Also acts on benzyl (2S,3S)-2-methyl-3-hydroxybutanoate; otherwise highly specific. Benzyl (2R,3S)-2-methyl-3-hydroxybutanoate + NADP(+) = benzyl 2-methyl-3-oxobutanoate + NADPH. Naloxone reductase Morphine 6-dehydrogenase In the reverse direction, also reduces naloxone to the 6-alpha-hydroxy analog. Activated by 2-mercaptoethanol. Also acts on some other alkaloids, including codeine, normorphine and ethylmorphine, but only very slowly on 7,8-saturated derivatives such as dihydromorphine and dihydrocodeine. Morphine + NAD(P)(+) = morphinone + NAD(P)H. Dihydroflavanol 4-reductase NADPH-dihydromyricetin reductase Dihydrokaempferol 4-reductase Dihydroflavonol 4-reductase Cis-3,4-leucopelargonidin + NADP(+) = (+)-dihydrokaempferol + NADPH. Involved in the biosynthesis of anthocyanidins in plants. NAD(+) can act instead of NADP(+), but more slowly. Also acts, in the reverse direction, on (+)-dihydroquercetin and (+)-dihydromyricetin; each dihydroflavonol is reduced to the corresponding cis-flavan-3,4-diol. UDP-glucose 6-dehydrogenase UDP-glucose + 2 NAD(+) + H(2)O = UDP-glucuronate + 2 NADH. Also acts on UDP-2-deoxyglucose. 6-pyruvoyltetrahydropterin 2'-reductase 6PPH4(2'-oxo) reductase 6-pyruvoyl-tetrahydropterin 2'-reductase Pyruvoyl-tetrahydropterin reductase 6-pyruvoyl tetrahydropterin (2'-oxo)reductase 6-lactoyl-5,6,7,8-tetrahydropterin + NADP(+) = 6-pyruvoyltetrahydropterin + NADPH. Not identical with EC 1.1.1.153. Vomifoliol 4'-dehydrogenase (+-)-6-hydroxy-3-oxo-alpha-ionol + NAD(+) = (+-)-6-hydroxy-3-oxo-alpha-ionone + NADH. Oxidizes vomifoliol to dehydrovomifoliol; involved in the metabolism of abscisic acid in Corynebacterium sp. (R)-4-hydroxyphenyllactate dehydrogenase (R)-aromatic lactate dehydrogenase Also acts, more slowly, on (R)-3-phenyllactate, (R)-3-(indol-3-yl)lactate and (R)-lactate. (R)-3-(4-hydroxyphenyl)lactate + NAD(P)(+) = 3-(4-hydroxyphenyl)pyruvate + NAD(P)H. Isopiperitenol dehydrogenase Involved in the biosynthesis of menthol and related monoterpenes in peppermint (Mentha piperita) leaves. (-)-trans-isopiperitenol + NAD(+) = (-)-isopiperitenone + NADH. Acts on (-)-trans-isopiperitenol, (+)-trans-piperitenol and (+)-trans-pulegol. NADPH-dependent M6P reductase Mannose-6-phosphate 6-reductase NADPH-mannose-6-P reductase D-mannitol 1-phosphate + NADP(+) = D-mannose 6-phosphate + NADPH. Involved in the biosynthesis of mannitol in celery (Apium graveolens) leaves. CDR Chlordecone reductase Chlordecone, an organochlorine pesticide, is 1,1a,3,3a,4,5,5a,5b,6-decachlorooctahydro-1,3,4-metheno-2H-cyclobuta[cd]pentalen-2-one. Chlordecone alcohol + NADP(+) = chlordecone + NADPH. 4-hydroxycyclohexanecarboxylate dehydrogenase The enzyme from Corynebacterium cyclohexanicum is highly specific for the trans-4-hydroxy derivative. Trans-4-hydroxycyclohexanecarboxylate + NAD(+) = 4-oxocyclohexanecarboxylate + NADH. (-)-borneol dehydrogenase (-)-borneol + NAD(+) = (-)-camphor + NADH. NADP(+) can also act, more slowly. (+)-sabinol dehydrogenase (+)-cis-sabinol + NAD(+) = (+)-sabinone + NADH. NADP(+) can also act, more slowly. Involved in the biosynthesis of (+)-3-thujone and (-)-3-isothujone. Diethyl 2-methyl-3-oxosuccinate reductase Also acts on diethyl (2S,3R)-2-methyl-3-hydroxysuccinate; and on the corresponding dimethyl esters. Diethyl (2R,3R)-2-methyl-3-hydroxysuccinate + NADP(+) = diethyl 2-methyl-3-oxosuccinate + NADPH. Histidinol dehydrogenase The Neurospora enzyme also catalyzes the reactions of EC 3.5.4.19 and EC 3.6.1.31. Also oxidizes L-histidinal. L-histidinol + 2 NAD(+) = L-histidine + 2 NADH. 3-alpha-hydroxyglycyrrhetinate dehydrogenase Highly specific to 3-alpha-hydroxy derivatives of glycyrrhetinate and its analogs. 3-alpha-hydroxyglycyrrhetinate + NADP(+) = 3-oxoglycyrrhetinate + NADPH. Not identical to EC 1.1.1.50. 15-hydroxyprostaglandin-I dehydrogenase (NADP(+)) PG I2 dehydrogenase Prostacyclin dehydrogenase (5Z,13E)-(15S)-6,9-alpha-epoxy-11-alpha,15-dihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-6,9-alpha-epoxy-11-alpha-hydroxy-15-oxoprosta-5,13-dienoate + NADPH. Specific for prostaglandin I(2). 15-hydroxyicosatetraenoate dehydrogenase (15S)-15-hydroxy-5,8,11-cis-13-trans-icosatetraenoate + NAD(P)(+) = 15-oxo-5,8,11-cis-13-trans-icosatetraenoate + NAD(P)H. N-acyl-D-mannosamine dehydrogenase N-acylmannosamine 1-dehydrogenase N-acylmannosamine dehydrogenase N-acetyl-D-mannosamine dehydrogenase Acts on acetyl-D-mannosamine and glycolyl-D-mannosamine. Highly specific. N-acyl-D-mannosamine + NAD(+) = N-acyl-D-mannosaminolactone + NADH. Flavanone 4-reductase Involved in the biosynthesis of 3-deoxyanthocyanidins from flavanones such as naringenin or eriodictyol. (2S)-flavan-4-ol + NADP(+) = (2S)-flavanone + NADPH. 8-oxocoformycin reductase B-specific with respect to NADPH. Coformycin + NADP(+) = 8-oxocoformycin + NADPH. Also reduces 8-oxodeoxy-coformycin to the nucleoside antibiotic deoxycoformycin. Tropinone reductase Pseudotropine forming tropinone reductase Tropinone reductase II Pseudotropine + NADP(+) = tropinone + NADPH. Hydroxyphenylpyruvate reductase Also acts on 3-(3,4-dihydroxyphenyl)lactate. Involved with EC 2.3.1.140 in the biosynthesis of rosmarinic acid. 3-(4-hydroxyphenyl)lactate + NAD(+) = 3-(4-hydroxyphenyl)pyruvate + NADH. 12-beta-hydroxysteroid dehydrogenase Acts on a number of bile acids, both in their free and conjugated forms. 3-alpha,7-alpha,12-beta-trihydroxy-5-beta-cholanate + NADP(+) = 3-alpha,7-alpha-dihydroxy-12-oxo-5-beta-cholanate + NADPH. 3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)) Also acts on other 17-beta-hydroxysteroids, on the 3-alpha-hydroxy group of pregnanes and bile acids, and on benzene dihydrodiol. Testosterone + NAD(+) = androst-4-ene-3,17-dione + NADH. Different from EC 1.1.1.50 or EC 1.1.1.213. Quinate:NAD oxidoreductase Quinic dehydrogenase Quinate:NAD(+) 5-oxidoreductase Quinate 5-dehydrogenase Quinate dehydrogenase The enzyme is specific for quinate as substrate; phenylpyruvate, phenylalanine, cinnamate and shikimate will not act as substrates. NAD(+) cannot be replaced by NADP(+). Quinate + NAD(+) = 3-dehydroquinate + NADH. N-acetylhexosamine 1-dehydrogenase Also acts on N-acetylgalactosamine and, more slowly, on N-acetylmannosamine. N-acetyl-D-glucosamine + NAD(+) = N-acetyl-D-glucosaminate + NADH. 6-endo-hydroxycineole dehydrogenase 6-endo-hydroxycineole + NAD(+) = 6-oxocineole + NADH. Carveol dehydrogenase (-)-trans-carveol + NADP(+) = (-)-carvone + NADPH. Methanol dehydrogenase Methanol + NAD(+) = formaldehyde + NADH. Cyclohexanol dehydrogenase Cyclohexanol + NAD(+) = cyclohexanone + NADH. Also oxidizes some other alicyclic alcohols and diols. Pterocarpin synthase Medicarpin + NADP(+) = vestitone + NADPH. Catalyzes the final step in the biosynthesis of the pterocarpin phytoalexins medicarpin and maackiain. Codeinone reductase (NADPH) Catalyzes the reversible reduction of codeinone to codeine, which is a direct precursor of morphine in the opium poppy plant, Papaver somniferum. Codeine + NADP(+) = codeinone + NADPH. Salutaridine reductase (NADPH) Salutaridinol + NADP(+) = salutaridine + NADPH. Catalyzes the reversible reduction of salutaridine to salutaridinol, which is a direct precursor of morphinan alkaloids in the poppy plant. Shikimate dehydrogenase Dehydroshikimic reductase Shikimate:NADP(+) 5-oxidoreductase DHS reductase Shikimate oxidoreductase 5-dehydroshikimic reductase Shikimate:NADP(+) oxidoreductase Shikimate 5-dehydrogenase 5-dehydroshikimate reductase Shikimate + NADP(+) = 3-dehydroshikimate + NADPH. In higher organisms, this enzyme forms part of a multienzyme complex with EC 4.2.1.10. NAD(+) cannot replace NADP(+). D-arabinitol 2-dehydrogenase (ribulose-forming) D-arabinitol 2-dehydrogenase D-arabinitol + NAD(+) = D-ribulose + NADH. Galactitol-1-phosphate 5-dehydrogenase Galactitol-1-phosphate + NAD(+) = L-tagatose 6-phosphate + NADH. Zinc Tetrahydroxynaphthalene reductase T4HN reductase Reduces 1,3,6,8-tetrahydroxynaphthalene to scytalone and also reduces 1,3,8-trihydroxynaphthalene to vermelone. Involved with EC 4.2.1.94 in the biosynthesis of melanin in pathogenic fungi. Scytalone + NADP(+) = 1,3,6,8-tetrahydroxynaphthalene + NADPH. D-carnitine dehydrogenase (S)-carnitine 3-dehydrogenase Specific for the (S)-enantiomer of carnitine, i.e., the enantiomer of the substrate of EC 1.1.1.108. (S)-carnitine + NAD(+) = 3-dehydrocarnitine + NADH. MTD Mannitol dehydrogenase NAD-dependent mannitol dehydrogenase The enzyme is specific for NAD(+) and does not use NADP(+). The enzyme from Apium graveolens (celery) oxidizes alditols with a minimum requirement of 2R chirality at the carbon adjacent to the primary carbon undergoing the oxidation. D-mannitol + NAD(+) = D-mannose + NADH. Fluoren-9-ol dehydrogenase Fluoren-9-ol + 2 NAD(P)(+) = fluoren-9-one + 2 NAD(P)H. Involved in the pathway for fluorene metabolism in Arthrobacter sp. 4-(hydroxymethyl)benzenesulfonate dehydrogenase 4-(hydroxymethyl)benzenesulfonate + NAD(+) = 4-formylbenzenesulfonate + NADH. Involved in the toluene-4-sulfonate degradation pathway in Comamonas testosteroni. 6-hydroxyhexanoate dehydrogenase 6-hydroxyhexanoate + NAD(+) = 6-oxohexanoate + NADH. Involved in the cyclohexanol degradation pathway in Acinetobacter NCIB 9871. 3-hydroxypimeloyl-CoA dehydrogenase 3-hydroxypimeloyl-CoA + NAD(+) = 3-oxopimeloyl-CoA + NADH. Involved in the anaerobic pathway of benzoate degradation in bacteria. NADH-dependent glyoxylate reductase Glycolate reductase Glyoxylic acid reductase Glyoxylate reductase Reduces glyoxylate to glycolate or hydroxypyruvate to D-glycerate. Glycolate + NAD(+) = glyoxylate + NADH. Sulcatone reductase Sulcatol + NAD(+) = sulcatone + NADH. Studies on the effects of growth-stage and nutrient supply on the stereochemistry of sulcatone reduction in Clostridia pasteurianum, C.tyrobutyricum and Lactobacillus brevis suggest that there may be at least two sulcatone reductases with different stereospecificities. Glycerol-1-phosphate dehydrogenase (NAD(P)(+)) sn-glycerol-1-phosphate + NAD(P)(+) = glycerone phosphate + NAD(P)H. Responsible for the formation of archaea-specific glycerophosphate and is stereospecifically different from EC 1.1.1.94. L-threonine 4-phosphate dehydrogenase 4-(phosphohydroxy)-L-threonine dehydrogenase 4-hydroxythreonine-4-phosphate dehydrogenase NAD(+)-dependent threonine 4-phosphate dehydrogenase The product of the reaction undergoes decarboxylation to give 3-amino-2-oxopropyl phosphate. 4-(phosphonooxy)-L-threonine + NAD(+) = (2S)-2-amino-3-oxo-4-phosphonooxybutanoate + NADH. In Escherichia coli, the coenzyme pyridoxal 5'-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72, EC 1.1.1.290, EC 2.6.1.52, EC 1.1.1.262, EC 2.6.99.2 and EC 1.4.3.5. 1,5-anhydro-D-fructose reductase AF reductase 1,5-anhydro-D-glucitol + NADP(+) = 1,5-anhydro-D-fructose + NADPH. Acetaldehyde, 2-dehydroglucose (glucosone) and glucuronate are poor substrates, but there is no detectable action on glucose, mannose and fructose. Also reduces pyridine-3-aldehyde and 2,3-butanedione. L-idonate 5-dehydrogenase The enzyme from Escherichia coli cannot oxidize D-gluconate to form 5-dehydrogluconate, a reaction that is catalyzed by EC 1.1.1.69. Zinc L-idonate + NAD(P)(+) = 5-dehydrogluconate + NAD(P)H. 3-methylbutanal reductase The enzyme purified from Saccharomyces cerevisiae catalyzes the reduction of a number of straight-chain and branched aldehydes, as well as some aromatic aldehydes. 3-methylbutanol + NAD(P)(+) = 3-methylbutanal + NAD(P)H. dTDP-4-keto-6-deoxyglucose reductase dTDP-4-dehydro-6-deoxyglucose reductase dTDP-D-fucose + NADP(+) = dTDP-4-dehydro-6-deoxy-D-glucose + NADPH. The enzyme from the Gram-negative bacterium Actinobacillus actinomycetemcomitans forms activated fucose for incorporation into capsular polysaccharide. 1-deoxy-D-xylulose-5-phosphate reductoisomerase DXP-reductoisomerase 1-deoxyxylulose-5-phosphate reductoisomerase 2-C-methyl-D-erythritol 4-phosphate + NADP(+) = 1-deoxy-D-xylulose 5-phosphate + NADPH. Manganese or cobalt or magnesium The enzyme from several eubacteria, including Escherichia coli, forms part of an alternative nonmevalonate pathway for terpenoid biosynthesis. 2-(R)-hydroxypropyl-CoM dehydrogenase 2-(2-(R)-hydroxypropylthio)ethanesulfonate dehydrogenase Forms component III of a four-component enzyme system (comprising EC 4.4.1.23 (component I), EC 1.8.1.5 (component II), EC 1.1.1.268 (component III) and EC 1.1.1.269 (component IV)) that is involved in epoxyalkane carboxylation in Xanthobacter sp. strain Py2. Highly specific for (R)-2-hydroxyalkyl thioethers of CoM, in contrast to EC 1.1.1.269, which is highly specific for the (S)-enantiomer. 2-(R)-hydroxypropyl-CoM + NAD(+) = 2-oxopropyl-CoM + NADH. 2-(S)-hydroxypropyl-CoM dehydrogenase 2-(2-(S)-hydroxypropylthio)ethanesulfonate dehydrogenase 2-(S)-hydroxypropyl-CoM + NAD(+) = 2-oxopropyl-CoM + NADH. Forms component IV of a four-component enzyme system (comprising EC 4.4.1.23 (component I), EC 1.8.1.5 (component II), EC 1.1.1.268 (component III) and EC 1.1.1.269 (component IV)) that is involved in epoxyalkane carboxylation in Xanthobacter sp. strain Py2. Highly specific for (S)-2-hydroxyalkyl thioethers of CoM, in contrast to EC 1.1.1.268, which is highly specific for the (R)-enantiomer. L-lactic acid dehydrogenase L-lactic dehydrogenase L-lactate dehydrogenase (S)-lactate + NAD(+) = pyruvate + NADH. http://purl.uniprot.org/mim/150100 Also oxidizes other (S)-2-hydroxymonocarboxylic acids. NADP(+) acts, more slowly, with the animal, but not the bacterial, enzyme. http://purl.uniprot.org/mim/150000 3-KSR 3-keto-steroid reductase Also acts on 5-alpha-cholest-7-en-3-one. 4-alpha-methyl-5-alpha-cholest-7-en-3-beta-ol + NADP(+) = 4-alpha-methyl-5-alpha-cholest-7-en-3-one + NADPH. GDP-fucose synthetase GDP-L-fucose synthase GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase GDP-L-fucose + NADP(+) = GDP-4-dehydro-6-deoxy-D-mannose + NADPH. Both human and Escherichia coli enzymes can use NADH in place of NADPH to a slight extent. (R)-sulfolactate:NAD(P)(+) oxidoreductase L-sulfolactate dehydrogenase (R)-2-hydroxyacid dehydrogenase (2R)-3-sulfolactate + NAD(P)(+) = 3-sulfopyruvate + NAD(P)H. This dehydrogenase also acts on (S)-malate and (S)-2-hydroxyglutarate i.e. with the same configuration as (R)-sulfolactate. Vellosimine dehydrogenase 10-deoxysarpagine + NADP(+) = vellosimine + NADPH. Also acts on related alkaloids with an endo-aldehyde group such as vellosimine (same stereochemistry at C-16) but only slight activity with exo-aldehydes (epimeric at C-16). Detected in many cell suspension cultures of plants from the family Apocynaceae. 2,5-didehydrogluconate reductase 2,5-diketo-D-gluconate reductase The identification of a bacterial beta-keto ester reductase as a 2,5-didehydrogluconate reductase links two previously separate areas of biocatalysis, i.e., asymmetric carbonyl reduction and microbial vitamin C production. Key enzyme in the microbial production of ascorbate. Can also reduce ethyl 2-methylacetoacetate stereoselectively to ethyl (2R)-methyl-(3S)-hydroxybutanoate and can also accept some other beta-keto esters. 2-dehydro-D-gluconate + NADP(+) = 2,5-didehydro-D-gluconate + NADPH. (+)-trans-carveol dehydrogenase Carveol dehydrogenase NADP(+) cannot replace NAD(+). Forms part of the monoterpenoid biosynthesis pathway in Carum carvi (caraway) seeds. (+)-trans-carveol + NAD(+) = (+)-(S)-carvone + NADH. Serine 3-dehydrogenase NAD(+) cannot replace NADP(+). L-serine + NADP(+) = 2-ammoniomalonate semialdehyde + NADPH. The product 2-ammoniomalonate semialdehyde is spontaneously converted into 2-aminoacetaldehyde and CO(2). 3-beta-hydroxy-5-beta-steroid dehydrogenase 3-beta-hydroxysteroid 5-beta-oxidoreductase 3-beta-hydroxysteroid 5-beta-progesterone oxidoreductase 3-beta-hydroxy-5-beta-pregnane-20-one + NADP(+) = 5-beta-pregnan-3,20-dione + NADPH. 3-beta-hydroxy-5-alpha-steroid dehydrogenase 3-beta-hydroxy-5-alpha-pregnane-20-one + NADP(+) = 5-alpha-pregnan-3,20-dione + NADPH. (R)-3-hydroxyacid-ester dehydrogenase 3-oxo ester (R)-reductase Also acts on ethyl (R)-3-oxobutanoate and some other (R)-3-hydroxy acid esters. Ethyl (R)-3-hydroxyhexanoate + NADP(+) = ethyl 3-oxohexanoate + NADPH. A subunit of Saccharomyces cerevisiae EC 2.3.1.86. Cf. EC 1.1.1.280. The (R)-symbol is allotted on the assumption that no substituents change the order of priority from O-3>C-2>C-4. D-lactate dehydrogenase D-lactic acid dehydrogenase D-lactic dehydrogenase (R)-lactate + NAD(+) = pyruvate + NADH. 3-oxo ester (S)-reductase (S)-3-hydroxyacid-ester dehydrogenase Cf. EC 1.1.1.279. Ethyl (S)-3-hydroxyhexanoate + NADP(+) = ethyl 3-oxohexanoate + NADPH. Also acts on 4-oxo-and 5-oxo-fatty acids and their esters. GDP-4-keto-6-deoxy-D-mannose reductase GDP-4-dehydro-6-deoxy-D-mannose reductase GDP-6-deoxy-D-lyxo-4-hexulose reductase GDP-6-deoxy-D-mannose + NAD(P)(+) = GDP-4-dehydro-6-deoxy-D-mannose + NAD(P)H. D-rhamnose is a constituent of lipopolysaccharides of Gram-negative plant and human pathogenic bacteria. Differs from EC 1.1.1.187 in that the only product formed is GDP-D-rhamnose (GDP-6-deoxy-D-mannose). Quinate/shikimate dehydrogenase (1) L-quinate + NAD(P)(+) = 3-dehydroquinate + NAD(P)H. This is the second shikimate dehydrogenase enzyme found in Escherichia coli and differs from EC 1.1.1.25, in that it can use both quinate and shikimate as substrate and either NAD(+) or NADP(+) as acceptor. (2) Shikimate + NAD(P)(+) = 3-dehydroshikimate + NAD(P)H. Methylglyoxal reductase (NADPH-dependent) Lactaldehyde dehydrogenase (NADP(+)) Lactaldehyde + NADP(+) = methylglyoxal + NADPH. It also acts on phenylglyoxal and glyoxal. It differs in coenzyme requirement from EC 1.1.1.78, which is found in mammals. The enzyme from the yeast Saccharomyces cerevisiae catalyzes the conversion of methylglyoxal into lactaldehyde; the reverse reaction has not been demonstrated. NAD- and glutathione-dependent formaldehyde dehydrogenase GD-FALDH ADH3 FDH S-(hydroxymethyl)glutathione dehydrogenase Formaldehyde dehydrogenase (glutathione) Chi-ADH Formaldehyde dehydrogenase NAD-linked formaldehyde dehydrogenase Glutathione-dependent formaldehyde dehydrogenase GS-FDH Class III alcohol dehydrogenase NAD-dependent formaldehyde dehydrogenase Formic dehydrogenase S-(hydroxymethyl)glutathione + NAD(P)(+) = S-formylglutathione + NAD(P)H. Also specifically reduces S-nitrosylglutathione. Forms part of the pathway that detoxifies formaldehyde, since the product is hydrolyzed by EC 3.1.2.12. The substrate, S-(hydroxymethyl)glutathione, forms spontaneously from glutathione and formaldehyde; its rate of formation is increased in some bacteria by the presence of EC 4.4.1.22. 3''-deamino-3''-oxonicotianamine reductase 2'-deoxymugineic acid + NAD(P)(+) = 3''-deamino-3''-oxonicotianamine + NAD(P)H. Homoisocitrate--isocitrate dehydrogenase Isocitrate--homoisocitrate dehydrogenase Potassium or ammonium May play a role in both the lysine and glutamate biosynthesis pathways. Manganese Unlike EC 1.1.1.41 and EC 1.1.1.87, this enzyme, from Pyrococcus horikoshii, can use both isocitrate and homoisocitrate as substrate. (1) Isocitrate + NAD(+) = 2-oxoglutarate + CO(2) + NADH. (2) (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD(+) = 2-oxoadipate + CO(2) + NADH. NADP(+)-dependent D-arabinitol dehydrogenase D-arabinitol dehydrogenase (NADP(+)) D-arabinitol dehydrogenase 1 (1) D-arabinitol + NADP(+) = D-xylulose + NADPH. D-arabinitol is capable of quenching reactive oxygen species involved in defense reactions of the host plant. This enzyme carries out the reactions of both EC 1.1.1.11 and EC 1.1.1.250, but unlike them, uses NADP(+) rather than NAD(+) as cofactor. The enzyme from the rust fungus Uromyces fabae can use D-arabinitol and D-mannitol as substrates in the forward direction and D-xylulose, D-ribulose and, to a lesser extent, D-fructose as substrates in the reverse direction. (2) D-arabinitol + NADP(+) = D-ribulose + NADPH. Xanthoxin oxidase Xanthoxin dehydrogenase Involved in the abscisic-acid biosynthesis pathway in plants, along with EC 1.2.3.14, EC 1.13.11.51 and EC 1.14.13.93. Molybdenum Xanthoxin + NAD(+) = abscisic aldehyde + NADH. NADP(+) cannot replace NAD(+) and short-chain alcohols such as ethanol, isopropanol, butanol and cyclohexanol cannot replace xanthoxin as substrate. Sorbose reductase This enzyme can also convert D-fructose into D-mannitol, but more slowly. D-glucitol + NADP(+) = L-sorbose + NADPH. The reaction occurs predominantly in the reverse direction. Glycerate dehydrogenase Hydroxypyruvate reductase Hydroxypyruvate dehydrogenase (R)-glycerate + NAD(+) = hydroxypyruvate + NADH. http://purl.uniprot.org/mim/260000 Erythronate-4-phosphate dehydrogenase 4-phosphoerythronate dehydrogenase 4-O-phosphoerythronate dehydrogenase 4PE dehydrogenase 4-phospho-D-erythronate + NAD(+) = (3R)-3-hydroxy-2-oxo-4-phosphonooxybutanoate + NADH. This enzyme catalyzes the second step in the biosynthesis of the coenzyme pyridoxal 5'-phosphate in Escherichia coli. Other enzymes involved in this pathway are EC 1.2.1.72, EC 2.6.1.52, EC 1.1.1.262, EC 2.6.99.2 and EC 1.4.3.5. The reaction occurs predominantly in the reverse direction. 2-hydroxymethylglutarate dehydrogenase (S)-2-hydroxymethylglutarate + NAD(+) = 2-formylglutarate + NADH. Other enzymes involved in this pathway are EC 1.17.1.5, EC 1.3.7.1, EC 3.5.2.18, EC 5.4.99.4, EC 5.3.3.6, EC 4.2.1.85 and EC 4.1.3.32. NADP(+) cannot replace NAD(+). Forms part of the nicotinate-fermentation catabolism pathway in Eubacterium barkeri. 1,5-anhydro-D-fructose reductase AFR 1,5-anhydro-D-fructose reductase (1,5-anhydro-D-mannitol-forming) In Sinorhizobium morelense, the product of the reaction, 1,5-anhydro-D-mannitol, can be further metabolized to D-mannose. Also reduces 1,5-anhydro-D-erythro-hexo-2,3-diulose and 2-ketoaldoses (called osones), such as D-glucosone (D-arabino-hexos-2-ulose) and 6-deoxy-D-glucosone. 1,5-anhydro-D-mannitol + NADP(+) = 1,5-anhydro-D-fructose + NADPH. Does not reduce common aldoses and ketoses, or non-sugar aldehydes and ketones. Differs from hepatic 1,5-anhydro-D-fructose reductase, which yields 1,5-anhydro-D-glucitol as the product (see EC 1.1.1.263). Present in some but not all Rhizobium species. Homoserine dehydrogenase The enzyme from Saccharomyces cerevisiae acts most rapidly with NAD(+); the Neurospora enzyme with NADP(+). L-homoserine + NAD(P)(+) = L-aspartate 4-semialdehyde + NAD(P)H. The enzyme from Escherichia coli is a multifunctional protein, which also catalyzes the reaction of EC 2.7.2.4. 3-hydroxybutyrate dehydrogenase D-beta-hydroxybutyrate dehydrogenase Also oxidizes other 3-hydroxymonocarboxylic acids. (R)-3-hydroxybutanoate + NAD(+) = acetoacetate + NADH. 3-hydroxyisobutyrate dehydrogenase 3-hydroxy-2-methylpropanoate + NAD(+) = 2-methyl-3-oxopropanoate + NADH. Mevaldate reductase (R)-mevalonate + NAD(+) = mevaldate + NADH. Mevaldate reductase (NADPH) (R)-mevalonate + NADP(+) = mevaldate + NADPH. May be identical with EC 1.1.1.2. 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMG-CoA reductase Hydroxymethylglutaryl-CoA reductase (NADPH) (R)-mevalonate + CoA + 2 NADP(+) = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH. The enzyme is inactivated by EC 2.7.11.31 and reactivated by EC 3.1.3.47. Beta-hydroxyacyl dehydrogenase Beta-keto-reductase 3-hydroxyacyl-CoA dehydrogenase http://purl.uniprot.org/mim/261515 (S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH. Broad specificity to acyl chain-length (cf. EC 1.1.1.211). http://purl.uniprot.org/mim/231530 Also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacylhydrolipoate. http://purl.uniprot.org/mim/609975 Some enzymes act, more slowly, with NADP(+). http://purl.uniprot.org/mim/300438 Acetoacetyl-CoA reductase (R)-3-hydroxyacyl-CoA + NADP(+) = 3-oxoacyl-CoA + NADPH. Malic dehydrogenase Malate dehydrogenase Also oxidizes some other 2-hydroxydicarboxylic acids. (S)-malate + NAD(+) = oxaloacetate + NADH. Malic enzyme Pyruvic-malic carboxylase NAD-malic enzyme Malate dehydrogenase (oxaloacetate-decarboxylating) (S)-malate + NAD(+) = pyruvate + CO(2) + NADH. Also decarboxylates added oxaloacetate. NAD-malic enzyme Pyruvic-malic carboxylase Malate dehydrogenase (decarboxylating) Malic enzyme Does not decarboxylate added oxaloacetate. (S)-malate + NAD(+) = pyruvate + CO(2) + NADH. 1-amino-2-propanol dehydrogenase Aminopropanol oxidoreductase 1-amino-2-propanol oxidoreductase Butylene glycol dehydrogenase D-aminopropanol dehydrogenase D-1-amino-2-propanol:NAD(2) oxidoreductase D-(-)-butanediol dehydrogenase D-butanediol dehydrogenase Diacetyl (acetoin) reductase D-1-amino-2-propanol dehydrogenase 2,3-butanediol dehydrogenase (R)-diacetyl reductase (R)-2,3-butanediol dehydrogenase (R,R)-butanediol dehydrogenase Butyleneglycol dehydrogenase (R,R)-butane-2,3-diol + NAD(+) = (R)-acetoin + NADH. Also converts diacetyl into acetoin with NADH as reductant. Pyruvic-malic carboxylase Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+)) NADP-malic enzyme Malic enzyme (S)-malate + NADP(+) = pyruvate + CO(2) + NADPH. Also decarboxylates added oxaloacetate. Nicotinamide adenine dinucleotide isocitrate dehydrogenase Isocitrate dehydrogenase (NAD(+)) Isocitric dehydrogenase IDH NAD isocitric dehydrogenase NAD-linked isocitrate dehydrogenase NAD isocitrate dehydrogenase NAD-specific isocitrate dehydrogenase Isocitric acid dehydrogenase Isocitrate dehydrogenase (NAD) NAD dependent isocitrate dehydrogenase Beta-ketoglutaric-isocitric carboxylase Unlike EC 1.1.1.42, oxalosuccinate cannot be used as a substrate. Manganese or magnesium The enzyme from some species can also use NADP(+) but much more slowly. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD(+)-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP(+)-linked enzyme that is found in both mitochondria and cytoplasm. Isocitrate + NAD(+) = 2-oxoglutarate + CO(2) + NADH. IDP Dual-cofactor-specific isocitrate dehydrogenase Isocitrate (nicotinamide adenine dinucleotide phosphate) dehydrogenase NADP(+)-ICDH Oxalosuccinate decarboxylase NADP isocitric dehydrogenase Oxalsuccinic decarboxylase NADP(+)-IDH Isocitrate (NADP) dehydrogenase Isocitrate dehydrogenase (NADP) NADP(+)-linked isocitrate dehydrogenase NADP-linked isocitrate dehydrogenase NADP-dependent isocitrate dehydrogenase Triphosphopyridine nucleotide-linked isocitrate dehydrogenase-oxalosuccinate carboxylase NADP-dependent isocitric dehydrogenase NADP-specific isocitrate dehydrogenase IDH Isocitrate dehydrogenase (NADP-dependent) Isocitrate dehydrogenase (NADP(+)) In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD(+)-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP(+)-linked enzyme that is found in both mitochondria and cytoplasm. Unlike EC 1.1.1.41, oxalosuccinate can be used as a substrate. (1) Isocitrate + NADP(+) = 2-oxoglutarate + CO(2) + NADPH. The enzyme from some species can also use NAD(+) but much more slowly. (2) Oxalosuccinate + NADP(+) = 2-oxoglutarate + CO(2) + NADPH. Manganese or magnesium 6-phosphogluconic dehydrogenase Phosphogluconate 2-dehydrogenase 6-phosphogluconate 2-dehydrogenase 6-phospho-D-gluconate + NAD(P)(+) = 6-phospho-2-dehydro-D-gluconate + NAD(P)H. 6-phosphogluconic dehydrogenase 6-phosphogluconic carboxylase Phosphogluconate dehydrogenase (decarboxylating) Phosphogluconic acid dehydrogenase 6PGD 6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO(2) + NADPH. http://purl.uniprot.org/mim/172200 L-3-aldonate dehydrogenase L-gulonate 3-dehydrogenase L-gulonate + NAD(+) = 3-dehydro-L-gulonate + NADH. Also oxidizes other L-3-hydroxyacids. L-arabinose 1-dehydrogenase L-arabinose + NAD(+) = L-arabinono-1,4-lactone + NADH. Glucose 1-dehydrogenase Beta-D-glucose + NAD(P)(+) = D-glucono-1,5-lactone + NAD(P)H. http://purl.uniprot.org/mim/604931 Also oxidizes D-xylose. Galactose 1-dehydrogenase D-galactose 1-dehydrogenase D-galactose + NAD(+) = D-galactono-1,4-lactone + NADH. G6PD Glucose-6-phosphate 1-dehydrogenase Certain preparations reduce NAD(+) as well as NADP(+). D-glucose 6-phosphate + NADP(+) = D-glucono-1,5-lactone 6-phosphate + NADPH. http://purl.uniprot.org/mim/305900 Also acts slowly on beta-D-glucose and other sugars. Acetoin dehydrogenase Diacetyl reductase Acetoin + NAD(+) = diacetyl + NADH. NADP(+) also acts. Hydroxyprostaglandin dehydrogenase 3-alpha-HSD 3-alpha-hydroxysteroid dehydrogenase (B-specific) Acts on other 3-alpha-hydroxysteroids and on 9-, 11-and 15-hydroxyprostaglandin. Androsterone + NAD(P)(+) = 5-alpha-androstane-3,17-dione + NAD(P)H. B-specific with respect to NAD(+) or NADP(+) (cf. EC 1.1.1.213). 3(or 17)-beta-hydroxysteroid dehydrogenase Also acts on other 3-beta-or 17-beta-hydroxysteroids (cf. EC 1.1.1.209). Testosterone + NAD(P)(+) = androst-4-ene-3,17-dione + NAD(P)H. 3-alpha-hydroxycholanate dehydrogenase 3-alpha-hydroxy-5-beta-cholanate + NAD(+) = 3-oxo-5-beta-cholanate + NADH. Also acts on other 3-alpha-hydroxysteroids with an acidic side-chain. 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase Cortisone reductase (R)-20-hydroxysteroid dehydrogenase The 3-alpha-hydroxy group or 20-beta-hydroxy group of pregnane and androstane steroids can act as donor. Androstan-3-alpha,17-beta-diol + NAD(+) = 17-beta-hydroxyandrostan-3-one + NADH. Allyl-alcohol dehydrogenase Also acts on saturated primary alcohols. Allyl alcohol + NADP(+) = acrolein + NADPH. Lactaldehyde reductase (NADPH) May be identical with EC 1.1.1.2. Propane-1,2-diol + NADP(+) = L-lactaldehyde + NADPH. Ribitol 2-dehydrogenase Ribitol + NAD(+) = D-ribulose + NADH. D-mannonate oxidoreductase Mannonic dehydrogenase Fructuronate reductase D-mannonate dehydrogenase Also reduces D-tagaturonate. D-mannonate + NAD(+) = D-fructuronate + NADH. Altronic oxidoreductase Altronate dehydrogenase Altronate oxidoreductase Tagaturonate dehydrogenase Tagaturonate reductase D-altronate + NAD(+) = D-tagaturonate + NADH. 3-hydroxypropionate dehydrogenase 3-hydroxypropanoate + NAD(+) = 3-oxopropanoate + NADH. NAD-linked glycerol dehydrogenase Glycerol dehydrogenase Also acts on 1,2-propanediol. Glycerol + NAD(+) = glycerone + NADH. 2-hydroxy-3-oxopropionate reductase Tartronate semialdehyde reductase (R)-glycerate + NAD(P)(+) = 2-hydroxy-3-oxopropanoate + NAD(P)H. 4-hydroxybutyrate dehydrogenase 4-hydroxybutanoate + NAD(+) = succinate semialdehyde + NADH. 17-beta-HSD 17-beta-hydroxysteroid dehydrogenase 17-beta-estradiol dehydrogenase Estrogen 17-oxidoreductase 20-alpha-hydroxysteroid dehydrogenase Estradiol 17-beta-dehydrogenase Also acts on (S)-20-hydroxypregn-4-en-3-one and related compounds, oxidizing the (S)-20-group. B-specific with respect to NAD(P)(+) (cf. EC 1.1.1.149). Estradiol-17-beta + NAD(P)(+) = estrone + NAD(P)H. 17-beta-HSD 17-ketoreductase Testosterone 17-beta-dehydrogenase Testosterone + NAD(+) = androst-4-ene-3,17-dione + NADH. 17-ketoreductase Testosterone 17-beta-dehydrogenase (NADP(+)) http://purl.uniprot.org/mim/264300 Also oxidizes 3-hydroxyhexobarbital to 3-oxohexobarbital. Testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH. PL reductase Pyridoxine 4-dehydrogenase Pyridoxal reductase Pyridoxine dehydrogenase Pyridoxin dehydrogenase Pyridoxine + NADP(+) = pyridoxal + NADPH. Also oxidizes pyridoxine phosphate. Omega-hydroxydecanoate dehydrogenase 10-hydroxydecanoate + NAD(+) = 10-oxodecanoate + NADH. Also acts, more slowly, on 9-hydroxynonanoate and 11-hydroxyundecanoate. Mannitol dehydrogenase Mannitol 2-dehydrogenase D-mannitol + NAD(+) = D-fructose + NADH. 5-keto-D-gluconate 5-reductase 5-ketogluconate reductase Gluconate 5-dehydrogenase 5-ketogluconate 5-reductase D-gluconate + NAD(P)(+) = 5-dehydro-D-gluconate + NAD(P)H. Propanediol-phosphate dehydrogenase Propane-1,2-diol 1-phosphate + NAD(+) = hydroxyacetone phosphate + NADH. Retinal reductase Alcohol dehydrogenase (NAD(P)(+)) Also reduces retinal to retinol. Reduces aliphatic aldehydes of chain length from C2 to C14, with greatest activity on C4, C6 and C8 aldehydes. An alcohol + NAD(P)(+) = an aldehyde + NAD(P)H. Glycerol dehydrogenase (NADP(+)) Glycerol + NADP(+) = D-glyceraldehyde + NADPH. Octanol dehydrogenase Acts, less rapidly, on other long-chain alcohols. 1-octanol + NAD(+) = 1-octanal + NADH. (R)-aminopropanol dehydrogenase (R)-1-aminopropan-2-ol + NAD(+) = aminoacetone + NADH. Potassium (S,S)-butanediol dehydrogenase (S,S)-butane-2,3-diol + NAD(+) = acetoin + NADH. Lactaldehyde reductase Propanediol oxidoreductase (1) (R)-propane-1,2-diol + NAD(+) = (R)-lactaldehyde + NADH. (2) (S)-propane-1,2-diol + NAD(+) = (S)-lactaldehyde + NADH. Methylglyoxal reductase D-lactaldehyde dehydrogenase Methylglyoxal reductase (NADH-dependent) This mammalian enzyme differs from the yeast enzyme, EC 1.1.1.283, in using NADH rather than NADPH as reductant. It oxidizes HO-CH(2)-CHOH-CHO (glyceraldehyde) as well as CH(3)-CHOH-CHO (lactaldehyde). (R)-lactaldehyde + NAD(+) = methylglyoxal + NADH. Glyoxylate reductase (NADP(+)) Has some affinity for NAD(+). Glycolate + NADP(+) = glyoxylate + NADPH. Also reduces hydroxypyruvate to glycerate. Glycerol 1-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase (NAD(+)) Glycerophosphate dehydrogenase (NAD) L-alpha-glycerophosphate dehydrogenase Alpha-glycerol phosphate dehydrogenase (NAD) NAD-L-glycerol-3-phosphate dehydrogenase NAD-alpha-glycerophosphate dehydrogenase NAD-linked glycerol 3-phosphate dehydrogenase Glycerol phosphate dehydrogenase (NAD) NAD-dependent glycerol phosphate dehydrogenase L-alpha-glycerol phosphate dehydrogenase Hydroglycerophosphate dehydrogenase L-glycerophosphate dehydrogenase NADH-dihydroxyacetone phosphate reductase L-glycerol phosphate dehydrogenase Alpha-glycerophosphate dehydrogenase (NAD) NAD-dependent glycerol-3-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase (NAD) sn-glycerol 3-phosphate + NAD(+) = glycerone phosphate + NADH. Also acts on propane-1,2-diol phosphate and glycerone sulfate (but with a much lower affinity). Isopropanol dehydrogenase (NADP(+)) Also acts on other short-chain secondary alcohols and, slowly, on primary alcohols. Propan-2-ol + NADP(+) = acetone + NADPH. D-glycerate dehydrogenase Hydroxypyruvate reductase D-glycerate + NAD(P)(+) = hydroxypyruvate + NAD(P)H. Malate dehydrogenase (NADP(+)) NADP-linked malate dehydrogenase (S)-malate + NADP(+) = oxaloacetate + NADPH. Activated by light. D-malate dehydrogenase (decarboxylating) (R)-malate + NAD(+) = pyruvate + CO(2) + NADH. Dimethylmalate dehydrogenase Manganese or cobalt Also acts on (R)-malate. (R)-3,3-dimethylmalate + NAD(+) = 3-methyl-2-oxobutanoate + CO(2) + NADH. Potassium or ammonia Beta-IPM dehydrogenase IMDH Beta-isopropylmalate dehydrogenase 3-isopropylmalate dehydrogenase 3-carboxy-2-hydroxy-4-methylpentanoate + NAD(+) = 3-carboxy-4-methyl-2-oxopentanoate + NADH. The product decarboxylates spontaneously to yield 4-methyl-2-oxopentanoate. Dihydroxyisovalerate dehydrogenase (isomerizing) Ketol-acid reductoisomerase Acetohydroxy acid isomeroreductase Alpha-keto-beta-hydroxylacyl reductoisomerase (1) (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH. (2) (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH. Homoisocitrate dehydrogenase (-)-1-hydroxy-1,2,4-butanetricarboxylate:NAD(+) oxidoreductase (decarboxylating) Homoisocitric dehydrogenase 2-hydroxy-3-carboxyadipate dehydrogenase 3-carboxy-2-hydroxyadipate dehydrogenase 3-carboxy-2-hydroxyadipate:NAD(+) oxidoreductase (decarboxylating) (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD(+) = 2-oxoadipate + CO(2) + NADH. Forms part of the lysine biosynthesis pathway in fungi. HMG-CoA reductase 3-hydroxy-3-methylglutaryl-coenzyme A reductase Beta-hydroxy-beta-methylglutaryl CoA-reductase Hydroxymethylglutaryl coenzyme A reductase Beta-hydroxy-beta-methylglutaryl coenzyme A reductase Hydroxymethylglutaryl-CoA reductase (R)-mevalonate + CoA + 2 NAD(+) = 3-hydroxy-3-methylglutaryl-CoA + 2 NADH. Xylitol dehydrogenase D-xylulose reductase Xylitol + NAD(+) = D-xylulose + NADH. Also acts as an L-erythrulose reductase. Aryl-alcohol dehydrogenase Benzyl alcohol dehydrogenase p-hydroxybenzyl alcohol dehydrogenase A group of enzymes with broad specificity toward primary alcohols with an aromatic or cyclohex-1-ene ring, but with low or no activity toward short-chain aliphatic alcohols. An aromatic alcohol + NAD(+) = an aromatic aldehyde + NADH. Aryl-alcohol dehydrogenase (NADP(+)) Also acts on some aliphatic aldehydes, but cinnamaldehyde was the best substrate found. An aromatic alcohol + NADP(+) = an aromatic aldehyde + NADPH. Oxaloglycolate reductase (decarboxylating) Also reduces hydroxypyruvate to D-glycerate and glyoxylate to glycolate. D-glycerate + NAD(P)(+) + CO(2) = 2-hydroxy-3-oxosuccinate + NAD(P)H. Tartrate dehydrogenase Mesotartrate dehydrogenase Monovalent cation (1) Tartrate + NAD(+) = oxaloglycolate + NADH. (2) Meso-tartrate + NAD(+) = oxaloglycolate + NADH. (3) (R,R)-tartrate + NAD(+) = oxaloglycolate + NADH. Manganese Glycerol-3-phosphate dehydrogenase (NAD(P)(+)) Glycerol phosphate dehydrogenase (nicotinamide adenine dinucleotide (phosphate)) Glycerol 3-phosphate dehydrogenase (NAD(P)) Glycerol 3-phosphate dehydrogenase (NADP) L-glycerol-3-phosphate:NAD(P) oxidoreductase The enzyme from Escherichia coli shows specificity for the B side of NADPH. sn-glycerol 3-phosphate + NAD(P)(+) = glycerone phosphate + NAD(P)H. Phosphoglycerate oxidoreductase PGDH Glycerate 3-phosphate dehydrogenase Phosphoglyceric acid dehydrogenase 3-phosphoglycerate dehydrogenase Glycerate-1,3-phosphate dehydrogenase Alpha-phosphoglycerate dehydrogenase Alpha-KG reductase 3PHP reductase 3-phosphoglyceric acid dehydrogenase Phosphoglycerate dehydrogenase D-3-phosphoglycerate dehydrogenase (2) 2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + NADH. The enzyme is unusual in that it also acts as a D-and L-2-hydroxyglutarate dehydrogenase (with the D-form being the better substrate) and as a 2-oxoglutarate reductase. (1) 3-phospho-D-glycerate + NAD(+) = 3-phosphonooxypyruvate + NADH. http://purl.uniprot.org/mim/601815 Reaction (1) occurs predominantly in the reverse direction and is inhibited by serine and glycine. Catalyzes the first committed step in the phosphoserine pathway of serine biosynthesis in Escherichia coli. Diiodophenylpyruvate reductase Substrates contain an aromatic ring with a pyruvate side chain. Compounds with hydroxy or amino groups in the 3 or 5 position are inactive. 3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD(+) = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + NADH. The most active substrates are halogenated derivatives. 3-hydroxybenzyl-alcohol dehydrogenase m-hydroxybenzyl alcohol dehydrogenase 3-hydroxybenzyl alcohol + NADP(+) = 3-hydroxybenzaldehyde + NADPH. (R)-2-hydroxy-fatty-acid dehydrogenase D-2-hydroxy fatty acid dehydrogenase (R)-2-hydroxystearate + NAD(+) = 2-oxostearate + NADH. (S)-2-hydroxy-fatty-acid dehydrogenase L-2-hydroxy fatty acid dehydrogenase (S)-2-hydroxystearate + NAD(+) = 2-oxostearate + NADH. With a cytochrome as acceptor Mannitol dehydrogenase (cytochrome) Polyol dehydrogenase D-mannitol + ferricytochrome c = D-fructose + ferrocytochrome c. Acts on polyols with a D-lyxo configuration, such as D-mannitol and D-sorbitol. L-lactate ferricytochrome c oxidoreductase L-lactate dehydrogenase (cytochrome) Cytochrome b2 Lactic acid dehydrogenase FMN (S)-lactate + 2 ferricytochrome c = pyruvate + 2 ferrocytochrome c + 2 H(+). Protoheme IX D-lactate dehydrogenase (cytochrome) Lactic acid dehydrogenase D-lactate ferricytochrome c oxidoreductase FAD (R)-lactate + 2 ferricytochrome c = pyruvate + 2 ferrocytochrome c. D-lactate dehydrogenase (cytochrome c-553) From Desulfovibrio vulgaris. (R)-lactate + 2 ferricytochrome c-553 = pyruvate + 2 ferrocytochrome c-553. With oxygen as acceptor Pyranose oxidase Glucose 2-oxidase Also oxidizes D-xylose, L-sorbose and D-glucono-1,5-lactone, which have the same ring conformation and configuration at C-2, C-3 and C-4. D-glucose + O(2) = 2-dehydro-D-glucose + H(2)O(2). FAD L-sorbose oxidase 2,6-dichloroindophenol can act as acceptor. Also acts on D-glucose, D-galactose and D-xylose, but not on D-fructose. L-sorbose + O(2) = 5-dehydro-D-fructose + H(2)O(2). Pyridoxin 4-oxidase Pyridoxine 4-oxidase 2,6-dichloroindophenol can act as acceptor. FAD Pyridoxine + O(2) = pyridoxal + H(2)O(2). AOX Alcohol oxidase Methanol oxidase Acts on lower primary alcohols and unsaturated alcohols but branched-chain and secondary alcohols are not attacked. FAD A primary alcohol + O(2) = an aldehyde + H(2)O(2). Catechol oxidase (dimerizing) 4 catechol + 3 O(2) = 2 dibenzo[1,4]dioxin-2,3-dione + 6 H(2)O. Hydroxy-acid oxidase A (S)-2-hydroxy-acid oxidase Glycolate oxidase Hydroxy-acid oxidase B FMN (S)-2-hydroxy acid + O(2) = 2-oxo acid + H(2)O(2). The rat isoenzyme B also acts as EC 1.4.3.2. Exists as two major isoenzymes; the A form preferentially oxidizes short-chain aliphatic hydroxy acids; the B form preferentially oxidizes long-chain and aromatic hydroxy acids. Ecdysone oxidase 2,6-dichloroindophenol can act as acceptor. Ecdysone + O(2) = 3-dehydroecdysone + H(2)O(2). Choline oxidase Also oxidizes betaine aldehyde to betaine. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 and EC 2.1.1.157. Different enzymes are involved in the first reaction. In many bacteria, plants and animals, betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. The enzyme involved in the second step, EC 1.2.1.8, appears to be the same in plants, animals and bacteria. In plants, this reaction is catalyzed by EC 1.14.15.7, whereas in animals and many bacteria, it is catalyzed by either membrane-bound choline dehydrogenase (EC 1.1.99.1) or soluble choline oxidase (EC 1.1.3.17). FAD Choline + O(2) = betaine aldehyde + H(2)O(2). Secondary-alcohol oxidase Acts on secondary alcohols with five or more carbons, and polyvinyl alcohols with molecular mass over 300 Da. Iron A secondary alcohol + O(2) = a ketone + H(2)O(2). 4-hydroxymandelate oxidase FAD (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate + O(2) = 4-hydroxybenzaldehyde + CO(2) + H(2)O(2). Manganese Long-chain-alcohol oxidase 2 long-chain alcohol + O(2) = 2 long-chain aldehyde + 2 H(2)O. Oxidizes long-chain fatty alcohols; best substrate is dodecyl alcohol. Alpha-glycerophosphate oxidase Glycerol-3-phosphate oxidase sn-glycerol 3-phosphate + O(2) = glycerone phosphate + H(2)O(2). FAD Thiamine oxidase Thiamine dehydrogenase The product differs from thiamine in replacement of -CH(2)-CH(2)-OH by -CH(2)-COOH; the two-step oxidation proceeds without the release of the intermediate aldehyde from the enzyme. FAD Thiamine + 2 O(2) + H(2)O = thiamine acetic acid + 2 H(2)O(2). Hydroxyphytanate oxidase L-2-hydroxyphytanate + O(2) = 2-oxophytanate + H(2)O(2). Nucleoside oxidase Other purine and pyrimidine nucleosides (as well as 2'-deoxynucleosides) are substrates, but ribose and nucleotides are not substrates. Inosine + O(2) = 9-riburonosylhypoxanthine + 2 H(2)O. The overall reaction takes place in two separate steps: (1) 2 inosine + O(2) = 2 5'-dehydroinosine + 2 H(2)O. (2) 2 5'-dehydroinosine + O(2) = 2 9-riburonosylhypoxanthine + 2 H(2)O. Differs from EC 1.1.3.39 as it produces water rather than hydrogen peroxide. The 5'-dehydro nucleoside is being released from the enzyme to serve as substrate for the second reaction. N-acylhexosamine oxidase Also acts on N-glycolylglucosamine, N-acetylgalactosamine and, more slowly, on N-acetylmannosamine. N-acetyl-D-glucosamine + O(2) = N-acetyl-D-glucosaminate + H(2)O(2). Malate oxidase Malic oxidase (S)-malate + O(2) = oxaloacetate + H(2)O(2). FAD Polyvinyl-alcohol oxidase PVA oxidase Polyvinyl alcohol + O(2) = oxidized polyvinyl alcohol + H(2)O(2). D-arabinono-1,4-lactone oxidase FAD D-arabinono-1,4-lactone + O(2) = D-erythro-ascorbate + H(2)O(2). 4-hydroxy-2-methoxybenzyl alcohol oxidase Vanillyl-alcohol oxidase Vanillyl alcohol + O(2) = vanillin + H(2)O(2). Converts a wide range of 4-hydroxybenzyl alcohols and 4-hydroxybenzylamines into the corresponding aldehydes. The allyl group of 4-allylphenols is also converted into the -CH=CH-CH(2)OH group. FAD Nucleoside oxidase (H(2)O(2)-forming) Differs from EC 1.1.3.28 as it produces hydrogen peroxide rather than water. Other purine and pyrimidine nucleosides (as well as 2'-deoxynucleosides and arabinosides) are substrates, but ribose and nucleotides are not substrates. Adenosine + 2 O(2) = 9-riburonosyladenine + 2 H(2)O(2). The overall reaction takes place in two separate steps: (1) Adenosine + O(2) = 5'-dehydroadenosine + H(2)O(2). (2) 5'-dehydroadenosine + O(2) = 9-riburonosyladenine + H(2)O(2). Heme The 5'-dehydro nucleoside is being released from the enzyme to serve as substrate for the second reaction. FAD Beta-D-glucose:oxygen 1-oxido-reductase Glucose oxyhydrase GOD Glucose aerodehydrogenase Glucose oxidase D-glucose-1-oxidase FAD Beta-D-glucose + O(2) = D-glucono-1,5-lactone + H(2)O(2). D-arabinitol oxidase D-mannitol oxidase Mannitol oxidase Also catalyzes the oxidation of D-arabinitol and, to a lesser extent, D-glucitol (sorbitol), whereas L-arabinitol is not a good substrate. Mannitol + O(2) = mannose + H(2)O(2). The enzyme from the snails Helix aspersa and Arion ater is found in a specialized tubular organelle that has been termed the mannosome. Xylitol oxidase The enzyme also oxidizes D-sorbitol. Xylitol + O(2) = xylose + H(2)O(2). FAD Hexose oxidase Also oxidizes D-galactose, D-mannose, maltose, lactose and cellobiose. Copper Beta-D-glucose + O(2) = D-glucono-1,5-lactone + H(2)O(2). Cholesterol-O(2) oxidoreductase Cholesterol oxidase Cholesterol + O(2) = cholest-4-en-3-one + H(2)O(2). FAD Veratryl alcohol oxidase Aryl-alcohol oxidase An aromatic primary alcohol + O(2) = an aromatic aldehyde + H(2)O(2). Oxidizes many primary alcohols containing an aromatic ring; best substrates are (2-naphthyl)methanol and 3-methoxybenzyl alcohol. L-gulonolactone oxidase L-gulono-gamma-lactone oxidase GLO The product spontaneously isomerizes to L-ascorbate. (1) L-gulono-1,4-lactone + O(2) = L-xylo-hex-2-ulono-1,4-lactone + H(2)O(2). FAD While most higher animals can synthesize ascorbic acid, primates and guinea pigs cannot. (2) L-xylo-hex-2-ulono-1,4-lactone = L-ascorbate. Galactose oxidase Beta-galactose oxidase D-galactose + O(2) = D-galacto-hexodialdose + H(2)O(2). Copper With a disulfide as acceptor Vitamin K1 epoxide reductase Phylloquinone epoxide reductase Vitamin-K-epoxide reductase (warfarin-sensitive) In the reverse reaction, vitamin K 2,3-epoxide is reduced to vitamin K and possibly to vitamin K hydroquinone by 1,4-dithioerythritol, which is oxidized to a disulfide; some other dithiols and 4-butanethiol can also act. 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol. Inhibited strongly by warfarin (cf. EC 1.1.4.2). Vitamin K 2,3-epoxide reductase Vitamin-K-epoxide reductase (warfarin-insensitive) Not inhibited by warfarin (cf. EC 1.1.4.1). In the reverse reaction, vitamin K 2,3-epoxide is reduced to 3-hydroxy-(and 2-hydroxy-) vitamin K by 1,4-dithioerythritol, which is oxidized to a disulfide. 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol. With a quinone or similar compound as acceptor Glucose dehydrogenase (PQQ-dependent) Glucose dehydrogenase (pyrroloquinoline-quinone) Quinoprotein glucose dehydrogenase D-glucose:(pyrroloquinoline-quinone) 1-oxidoreductase Quinoprotein D-glucose dehydrogenase Magnesium or calcium This is a PQQ-containing quinoprotein that catalyzes a direct oxidation of D-glucose to D-gluconate in the periplasm of some bacteria and concomitantly transfers electrons to ubiquinol oxidase through ubiquinone in the respiratory chain. D-glucose + ubiquinone = D-glucono-1,5-lactone + ubiquinol. PQQ With other acceptors Choline-cytochrome c reductase Choline oxidase Choline dehydrogenase PQQ Choline + acceptor = betaine aldehyde + reduced acceptor. In many bacteria, plants and animals, betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. In plants, this reaction is catalyzed by EC 1.14.15.7, whereas in animals and many bacteria, it is catalyzed by either membrane-bound choline dehydrogenase (EC 1.1.99.1) or soluble choline oxidase (EC 1.1.3.17). In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 and EC 2.1.1.157. Different enzymes are involved in the first reaction. The enzyme involved in the second step, EC 1.2.1.8, appears to be the same in plants, animals and bacteria. Glucose dehydrogenase (acceptor) Glucose dehydrogenase (Aspergillus) D-glucose + acceptor = D-glucono-1,5-lactone + reduced acceptor. FAD 2,6-dichloroindophenol can act as acceptor. Fructose 5-dehydrogenase D-fructose dehydrogenase 2,6-dichloroindophenol can act as acceptor. D-fructose + acceptor = 5-dehydro-D-fructose + reduced acceptor. Sorbose dehydrogenase 2,6-dichloroindophenol can act as acceptor. L-sorbose + acceptor = 5-dehydro-D-fructose + reduced acceptor. D-aldohexopyranoside dehydrogenase Glucoside 3-dehydrogenase The enzyme acts on D-glucose, D-galactose, D-glucosides and D-galactosides, but D-glucosides react more rapidly than D-galactosides. FAD Sucrose + acceptor = 3-dehydro-alpha-D-glucosyl-beta-D-fructofuranoside + reduced acceptor. Glycolic acid dehydrogenase Glycolate dehydrogenase Glycolate oxidoreductase Also acts on (R)-lactate. Glycolate + acceptor = glyoxylate + reduced acceptor. 2,6-dichloroindophenol and phenazine methosulfate can act as acceptors. Malate dehydrogenase (acceptor) FAD (S)-malate + acceptor = oxaloacetate + reduced acceptor. Cellobiose dehydrogenase Cellobiose oxidase CBOR Cellobiose oxidoreductase CDH Cellobiose dehydrogenase (quinone) Cellobiose dehydrogenase (acceptor) Cellobiose-quinone oxidoreductase The enzyme from the white rot fungus Phanerochaete chrysosporium is unusual in having two redoxin domains, one containing a flavin and the other a protoheme group. Cellobiose + acceptor = cellobiono-1,5-lactone + reduced acceptor. 2,6-dichloroindophenol can act as acceptor. FAD Heme Also acts, more slowly, on cello-oligosaccharides, lactose and D-glucosyl-1,4-beta-D-mannose. Includes EC 1.1.5.1, which is now known to be a proteolytic product of this enzyme. It transfers reducing equivalents from cellobiose to two types of redox acceptor: two-electron oxidants, including redox dyes, benzoquinones and molecular oxygen and one-electron oxidants, including semiquinone species, Fe(2+) complexes and the model acceptor cytochrome c. L-alpha-hydroxyglutarate dehydrogenase Hydroxyglutaric dehydrogenase 2-hydroxyglutarate dehydrogenase Alpha-hydroxyglutarate dehydrogenase Alpha-ketoglutarate reductase Alpha-hydroxyglutarate oxidoreductase FAD (S)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor. http://purl.uniprot.org/mim/236792 Polyethylene glycol dehydrogenase Alkan-1-ol dehydrogenase (acceptor) Primary alcohol + acceptor = aldehyde + reduced acceptor. PQQ 2,6-dichloroindophenol can act as acceptor. Acts on C(3)-C(16) linear-chain saturated primary alcohols, C(4)-C(7) aldehydes and on non-ionic surfactants containing polyethylene glycol residues, such as Tween 40 and 60, but not on methanol and only very slowly on ethanol. D-sorbitol dehydrogenase (acceptor) FAD D-sorbitol + acceptor = L-sorbose + reduced acceptor. Glycerol dehydrogenase (acceptor) PQQ Glycerol + acceptor = glycerone + reduced acceptor. Also acts, more slowly, on a number of other polyols including D-sorbitol, D-arabinitol, meso-erythritol, adonitol and propylene glycol. Polyvinyl-alcohol dehydrogenase (acceptor) PVA dehydrogenase Polyvinyl alcohol + acceptor = oxidized polyvinyl alcohol + reduced acceptor. Phenazine methosulfate and 2,6-dichloroindophenol can act as acceptors. Also acts, more slowly, on 2-hexanol and some other secondary alcohols (cf. EC 1.1.99.8 and EC 1.1.99.20). PQQ Hydroxyacid--oxoacid transhydrogenase (S)-3-hydroxybutanoate + 2-oxoglutarate = acetoacetate + (R)-2-hydroxyglutarate. 4-hydroxybutanoate and (R)-2-hydroxyglutarate can also act as donors; 4-oxobutanoate can also act as acceptor. Quinate dehydrogenase (pyrroloquinoline-quinone) NAD(P)-independent quinate dehydrogenase Quinate:pyrroloquinoline-quinone 5-oxidoreductase Quinate + pyrroloquinoline-quinone = 3-dehydroquinate + reduced pyrroloquinoline-quinone. 3-hydroxycyclohexanone dehydrogenase 2,6-dichloroindophenol and methylene blue can act as acceptors. 3-hydroxycyclohexanone + acceptor = cyclohexane-1,3-dione + reduced acceptor. (R)-pantoyllactone dehydrogenase (flavin) 2-dehydropantolactone reductase (flavin) 2-dehydropantoyl-lactone reductase (flavin) (R)-pantolactone dehydrogenase (flavin) High specificity for (R)-pantolactone. FMN Phenazine methosulfate (PMS) can act as acceptor. The enzyme has been studied in Nocardia asteroides and shown to be membrane-bound and induced by 1,2-propanediol. (R)-pantolactone + acceptor = 2-dehydropantolactone + reduced acceptor. Glucose--fructose oxidoreductase D-mannose, D-xylose, D-galactose, 2-deoxy-D-glucose and L-arabinose will function as aldose substrates, but with low affinities. Xylulose and glycerone (dihydroxyacetone) will replace fructose, but they are poor substrates. The apparent affinity for fructose is low, because little of the fructose substrate is in the open-chain form. D-glucose + D-fructose = D-gluconolactone + D-glucitol. The enzyme from Zymomonas mobilis contains tightly bound NADP(+). The ketose substrate must be in the open-chain form. Pyranose dehydrogenase Pyranose dehydrogenase (acceptor) Quinone-dependent pyranose dehydrogenase Pyranose-quinone oxidoreductase PDH (2) Pyranose + acceptor = 3-dehydropyranose + reduced acceptor. (3) Pyranose + acceptor = 2,3-dehydropyranose + reduced acceptor. A number of aldoses and ketoses in pyranose form, as well as glycosides, gluco-oligosaccharides, sucrose and lactose can act as a donor. FAD The enzyme also acts on 1->4-alpha-and 1->4-beta-gluco-oligosaccharides, non-reducing gluco-oligosaccharides and L-arabinose, which are not substrates of EC 1.1.3.10. D-glucose is exclusively or preferentially oxidized at C-3 (depending on the enzyme source), but can also be oxidized at C-2 + C-3. (5) A pyranoside + acceptor = a 3,4-dehydropyranoside + reduced acceptor. (4) A pyranoside + acceptor = a 3-dehydropyranoside + reduced acceptor. 1,4-benzoquinone or ferricenium ion (ferrocene oxidized by removal of one electron) can serve as acceptor. Unlike EC 1.1.3.10, this fungal enzyme does not interact with O(2) and exhibits extremely broad substrate tolerance with variable regioselectivity (C-3, C-2 or C-3 + C-2 or C-3 + C-4) for (di)oxidation of different sugars. (1) Pyranose + acceptor = 2-dehydropyranose + reduced acceptor. Sugars are oxidized in their pyranose but not in their furanose form. Gluconate 2-dehydrogenase (acceptor) FAD D-gluconate + acceptor = 2-dehydro-D-gluconate + reduced acceptor. 2-oxoacid reductase HVOR (2R)-hydroxycarboxylate-viologen-oxidoreductase 2-oxo-acid reductase Mononucleotide molybdenum (pyranopterin) cofactor The enzyme from Proteus sp. is inactivated by oxygen. Branching in a substrate at the C-3 position results in loss of activity. A (2R)-hydroxy-carboxylate + acceptor = a 2-oxo-carboxylate + reduced acceptor. Iron-sulfur Has broad substrate specificity, with 2-oxo-monocarboxylates and 2-oxo-dicarboxylates acting as substrates. MDH (S)-mandelate dehydrogenase L(+)-mandelate dehydrogenase Transfers the electron pair from FMNH(2) to a component of the electron transport chain, most probably ubiquinone. It also prefers substrates that, like (S)-mandelate, have beta unsaturation, e.g. (indol-3-yl)glycolate compared with (indol-3-yl)lactate. (S)-2-hydroxy-2-phenylacetate + acceptor = 2-oxo-2-phenylacetate + reduced acceptor. Has a large active-site pocket and preferentially binds substrates with longer sidechains, e.g. 2-hydroxyoctanoate rather than 2-hydroxybutyrate. While all enzymes of this family oxidize the (S)-enantiomer of an alpha-hydroxy acid to an alpha-oxo acid, the ultimate oxidant (oxygen, intramolecular heme or some other acceptor) depends on the particular enzyme. Esters of mandelate, such as methyl (S)-mandelate, are also substrates. It is part of a metabolic pathway in Pseudomonads that allows these organisms to utilize mandelic acid, derivatized from the common soil metabolite amygdalin, as the sole source of carbon and energy. Dehydrogluconate dehydrogenase Ketogluconate dehydrogenase 2-dehydro-D-gluconate + acceptor = 2,5-didehydro-D-gluconate + reduced acceptor. Flavoprotein Glycerol-3-phosphate dehydrogenase Flavin sn-glycerol 3-phosphate + acceptor = glycerone phosphate + reduced acceptor. D-2-hydroxy-acid dehydrogenase (R)-lactate + acceptor = pyruvate + reduced acceptor. Acts on a variety of (R)-2-hydroxy acids. FAD Zinc Lactate--malate transhydrogenase (S)-lactate + oxaloacetate = pyruvate + malate. Contains tightly bound nicotinamide nucleotide in its active center. Catalyzes hydrogen transfer from C(3) or C(4) (S)-2-hydroxy acids to 2-oxo acids. This prosthetic group cannot be removed without denaturation of the protein. Methanol dehydrogenase Alcohol dehydrogenase (acceptor) Acts on a wide range of primary alcohols, including methanol. PQQ A primary alcohol + acceptor = an aldehyde + reduced acceptor. Pyridoxol 5-dehydrogenase Pyridoxine 5-dehydrogenase Pyridoxine + acceptor = isopyridoxal + reduced acceptor. FAD Acting on diphenols and related substances as donors With NAD(+) or NADP(+) as acceptor Trans-acenaphthene-1,2-diol dehydrogenase (+-)-trans-acenaphthene-1,2-diol + 2 NADP(+) = acenaphthenequinone + 2 NADPH. Some preparations also utilize NAD(+). With a cytochrome as acceptor L-ascorbate--cytochrome-b5 reductase L-ascorbate + ferricytochrome b5 = monodehydroascorbate + ferrocytochrome b5 + H(+). Ubiquinone--cytochrome-c oxidoreductase Complex III (mitochondrial electron transport) Cytochrome bc1 complex Ubiquinol--cytochrome-c reductase Depending on the organism and physiological conditions, either two or four protons are extruded from the cytoplasmic to the non-cytoplasmic compartment (cf. EC 1.6.99.3). QH(2) + 2 ferricytochrome c = Q + 2 ferrocytochrome c + 2 H(+). Contains cytochrome b-562, cytochrome b-566, cytochrome c1, and 2-iron ferredoxin. With oxygen as acceptor Catechol oxidase o-diphenolase Diphenol oxidase Polyphenol oxidase Phenolase Tyrosinase Copper Many of these enzymes also catalyze the reaction listed under EC 1.14.18.1; this is especially true for the classical tyrosinase. Also acts on a variety of substituted catechols. 2 catechol + O(2) = 2 1,2-benzoquinone + 2 H(2)O. Laccase Urishiol oxidase The semiquinone may react further either enzymically or non-enzymically. A group of multi-copper proteins of low specificity. Copper 4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O. Acts on both o-and p-quinols, and often acting also on aminophenols and phenylenediamine. Ascorbase L-ascorbate oxidase Copper 2 L-ascorbate + O(2) = 2 dehydroascorbate + 2 H(2)O. o-aminophenol oxidase Isophenoxazine synthase Flavoprotein Copper or manganese Two molecules of the product 6-iminocyclohexa-2,4-dienone (i.e. 1,2-benzoquinone monoimine) spontaneously condense with oxidation to yield 2-aminophenoxazin-3-one. While the enzyme from the plant Tecoma stans is activated by Mn(2+), that from the bacterium Streptomyces griseus (GriF) requires Cu(2+) for maximal activity. 3-amino-4-hydroxybenzaldehyde, which has a -CHO group at the para-position with respect to the hydroxy group of 2-aminophenol, was found to be the best substrate for GriF. 2 2-aminophenol + O(2) + oxidant = 2-aminophenoxazin-3-one + 2 H(2)O + reduced oxidant. 3-hydroxyanthranilate oxidase 3-hydroxyanthranilic acid oxidase 3-hydroxyanthranilate + O(2) = 6-imino-5-oxocyclohexa-1,3-dienecarboxylate + H(2)O(2). Rifamycin-B oxidase Also acts on benzene-1,4-diol and, more slowly, on some other p-quinols. Rifamycin B + O(2) = rifamycin O + H(2)O(2). Not identical with EC 1.10.3.1, EC 1.10.3.2, EC 1.10.3.4 or EC 1.10.3.5. With other acceptors Plastoquinol--plastocyanin reductase Cytochrome b6f complex A cytochrome f,b6 complex separated from chloroplasts. Plastoquinol-1 + 2 oxidized plastocyanin = plastoquinone + 2 reduced plastocyanin. Cytochrome c-552 can act instead of plastocyanin, but more slowly. Also acts, more slowly, on plastoquinol-9 and ubiquinols. NAD(P)H:quinone oxidoreductase 2 Ribosyldihydronicotinamide dehydrogenase (quinone) N-ribosyldihydronicotinamide dehydrogenase (quinone) NQO(2) Quinone reductase 2 NRH:quinone oxidoreductase 2 QR2 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone = 1-(beta-D-ribofuranosyl)nicotinamide + a hydroquinone. FAD This enzyme can catalyze both 2-electron and 4-electron reductions, but one-electron acceptors, such as potassium ferricyanide, cannot be reduced. Polycyclic aromatic hydrocarbons, such as benz[a]anthracene, and the estrogens 17-beta-estradiol and diethylstilbestrol are potent inhibitors, but dicoumarol is only a very weak inhibitor. Zinc Unlike EC 1.6.5.2, this quinone reductase cannot use NADH or NADPH; instead it uses N-ribosyl-and N-alkyldihydronicotinamides. VDE Violaxanthin de-epoxidase It is activated by a low pH of the thylakoid lumen (produced by high light intensity). Zeaxanthin induces the dissipation of excitation energy in the chlorophyll of the light-harvesting protein complex of photosystem II. Along with EC 1.14.13.90, this enzyme forms part of the xanthophyll (or violaxanthin) cycle for controlling the concentration of zeaxanthin in chloroplasts. (2) Antheraxanthin + ascorbate = zeaxanthin + dehydroascorbate + H(2)O. In higher plants the enzyme reacts with all-trans-diepoxides, such as violaxanthin, and all-trans-monoepoxides, but in the alga Mantoniella squamata, only the diepoxides are good substrates. (1) Violaxanthin + ascorbate = antheraxanthin + dehydroascorbate + H(2)O. Acting on a peroxide as acceptor Peroxidases NADH peroxidase NADH + H(2)O(2) = NAD(+) + 2 H(2)O. FAD Ferricyanide, quinones, etc., can replace H(2)O(2). Chloride peroxidase Chloroperoxidase Also acts on bromide and iodide. 2 RH + 2 Cl(-) + H(2)O(2) = 2 RCl + 2 H(2)O. Brings about the chlorination of a range of organic molecules, forming stable C-Cl bonds. Heme L-ascorbate peroxidase Ascorbic acid peroxidase L-ascorbate + H(2)O(2) = dehydroascorbate + 2 H(2)O. Phospholipid-hydroperoxide glutathione peroxidase Peroxidation-inhibiting protein Also acts on H(2)O(2), but much more slowly (cf. EC 1.11.1.9). The products of action of EC 1.13.11.12 on phospholipids can act as acceptor. Selenium 2 glutathione + a lipid hydroperoxide = glutathione disulfide + lipid + 2 H(2)O. Mn-dependent peroxidase Manganese peroxidase 2 Mn(2+) + 2 H(+) + H(2)O(2) = 2 Mn(3+) + 2 H(2)O. Involved in the oxidative degradation of lignin in white rot Basidiomycetes. Heme Diarylpropane oxygenase Ligninase I Lignin peroxidase LiP Diarylpropane peroxidase Involved in the oxidative breakdown of lignin in white rot basidiomycetes. Also oxidizes benzyl alcohols to aldehydes, via an aromatic cation radical. Heme Brings about the oxidative cleavage of C-C and ether (C-O-C) bonds in a number of lignin model compounds (of the diarylpropane and arylpropane-aryl ether type). Molecular oxygen may be involved in the reaction of some isoenzymes under aerobic conditions. 1,2-bis(3,4-dimethoxyphenyl)propane-1,3-diol + H(2)O(2) = 3,4-dimethoxybenzaldehyde + 1-(3,4-dimethoxyphenyl)ethane-1,2-diol + H(2)O. TrxPx Peroxiredoxin Tryparedoxin peroxidase TXNPx AhpC Prx Alkyl hydroperoxide reductase C22 Thioredoxin peroxidase PRDX In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond. The peroxidase reaction comprises two steps centered around a redox-active cysteine called the peroxidatic cysteine. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins. The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. To recycle the disulfide, known atypical 2-Cys Prxs appear to use thioredoxin as an electron donor. 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the 'resolving' cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants (R'-SH) (e.g. thioredoxin, AhpF, tryparedoxin or AhpD), completing the catalytic cycle. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid). The 1-Cys Prxs conserve only the peroxidatic cysteine, so that its oxidized form is directly reduced to cysteine by the reductant molecule. VP Hybrid peroxidase Polyvalent peroxidase Versatile peroxidase (1) Reactive Black 5 + H(2)O(2) = oxidized Reactive Black 5 + 2 H(2)O. Also able to oxidize phenols, hydroquinones and both low-and high-redox-potential dyes, due to a hybrid molecular architecture that involves multiple binding sites for substrates. (2) Donor + H(2)O(2) = oxidized donor + 2 H(2)O. This ligninolytic peroxidase combines the substrate-specificity characteristics of the two other ligninolytic peroxidases, EC 1.11.1.13 and EC 1.11.1.14. Heme NADPH peroxidase NADPH + H(2)O(2) = NADP(+) + 2 H(2)O. Fatty-acid peroxidase Acts on long-chain fatty acids from dodecanoic to octadecanoic acid. Palmitate + 2 H(2)O(2) = pentadecanal + CO(2) + 3 H(2)O. Cytochrome-c peroxidase 2 ferrocytochrome c + H(2)O(2) = 2 ferricytochrome c + 2 H(2)O. Heme Catalase 2 H(2)O(2) = O(2) + 2 H(2)O. http://purl.uniprot.org/mim/115500 A manganese protein containing Mn(3+) in the resting state, which also belongs here, is often called pseudocatalase. Heme Manganese This enzyme can also act as an EC 1.11.1.7 for which several organic substances, especially ethanol, can act as a hydrogen donor. Enzymes from some microorganisms, such as Penicillium simplicissimum, which exhibit both catalase and peroxidase activity, have sometimes been referred to as catalase-peroxidase. Myeloperoxidase Lactoperoxidase Peroxidase http://purl.uniprot.org/mim/261500 Donor + H(2)O(2) = oxidized donor + 2 H(2)O. http://purl.uniprot.org/mim/254600 Heme Thyroid peroxidase TPO Iodide peroxidase Iodotyrosine deiodase Thyroperoxidase Iodinase Iodotyrosine deiodinase Heme http://purl.uniprot.org/mim/274500 2 iodide + H(2)O(2) + 2 H(+) = 2 iodine + 2 H(2)O. Glutathione peroxidase 2 glutathione + H(2)O(2) = glutathione disulfide + 2 H(2)O. Selenium http://purl.uniprot.org/mim/138320 Steroid and lipid hydroperoxides, but not the product of reaction of EC 1.13.11.12 on phospholipids, can act as acceptor, but more slowly than H(2)O(2) (cf. EC 1.11.1.12). Acting on hydrogen as donor With NAD(+) or NADP(+) as acceptor Hydrogen dehydrogenase Hydrogenase Bidirectional hydrogenase NAD-linked hydrogenase H(2):NAD(+) oxidoreductase Iron-sulfur Nickel H(2) + NAD(+) = H(+) + NADH. FMN or FAD Hydrogen dehydrogenase (NADP(+)) NADP-reducing hydrogenase NADP-linked hydrogenase Flavoprotein H(2) + NADP(+) = H(+) + NADPH. Iron-sulfur With a cytochrome as acceptor Cytochrome-c3 hydrogenase H(2):ferricytochrome c3 oxidoreductase Cytochrome c3 reductase Cytochrome hydrogenase Some forms of the enzyme contain nickel ([NiFe]-hydrogenases) and, of these, some contain selenocysteine ([NiFeSe]-hydrogenases). Iron-sulfur Nickel Methylene blue and other acceptors can also be reduced. 2 H(2) + ferricytochrome c3 = 4 H(+) + ferrocytochrome c3. With a quinone or similar compound as acceptor Membrane-bound hydrogenase Hydrogen:quinone oxidoreductase Hydrogen-ubiquinone oxidoreductase Quinone-reactive Ni/Fe-hydrogenase Hydrogen:menaquinone oxidoreductase Also catalyzes the reduction of water-soluble quinones (e.g. 2,3-dimethylnaphthoquinone) or viologen dyes (benzyl viologen or methyl viologen) by H(2). H(2) + menaquinone = menaquinol. Iron-sulfur Nickel With an iron-sulfur protein as acceptor H(2) oxidizing hydrogenase Hydrogenase (ferredoxin) H(2) producing hydrogenase Hydrogenase I Uptake hydrogenase Hydrogenlyase Hydrogenase II Hydrogen-lyase Hydrogenase Bidirectional hydrogenase Ferredoxin hydrogenase H(2) + 2 oxidized ferredoxin = 2 reduced ferredoxin + 2 H(+). Nickel Iron-sulfur Can use molecular hydrogen for the reduction of a variety of substances. With other known acceptors Coenzyme F420-dependent hydrogenase Coenzyme F420 hydrogenase F420-reducing hydrogenase 8-hydroxy-5-deazaflavin-reducing hydrogenase The hydrogen acceptor coenzyme F420 is a deazaflavin derivative. FAD H(2) + coenzyme F420 = reduced coenzyme F420. The enzyme from some sources contains selenocysteine. Nickel The enzyme also reduces the riboflavin analog of F420, flavins and methylviologen, but to a lesser extent. Iron N(5),N(10)-methenyltetrahydromethanopterin hydrogenase H(2)-dependent methylene-H(4)MPT dehydrogenase H(2)-forming N(5),N(10)-methylenetetrahydromethanopterin dehydrogenase Hydrogen:N(5),N(10)-methenyltetrahydromethanopterin oxidoreductase Nonmetal hydrogenase 5,10-methenyltetrahydromethanopterin hydrogenase Does not contain nickel or iron-sulfur clusters. Does not catalyze the reduction of artificial dyes. Does not by itself catalyze a H(2)/H(+) exchange reaction. H(2) + 5,10-methenyltetrahydromethanopterin = H(+) + 5,10-methylenetetrahydromethanopterin. Methylviologen-reducing hydrogenase Methanophenazine hydrogenase Methanosarcina-phenazine hydrogenase H(2) + 2-(2,3-dihydropentaprenyloxy)phenazine = 2-dihydropentaprenyloxyphenazine. Iron-sulfur Nickel The enzyme from some sources contains selenocysteine. With other acceptors Hydrogenase (acceptor) Hydrogenlyase Uptake hydrogenase H(2) producing hydrogenase Hydrogen-lyase H(2) + A = AH(2). Iron-sulfur Uses molecular hydrogen for the reduction of a variety of substances. Nickel Acting on single donors with incorporation of molecular oxygen With incorporation of two atoms of oxygen Catechol 1,2-dioxygenase Pyrocatechase Catechase Iron Catechol + O(2) = cis,cis-muconate. Involved in the metabolism of nitro-aromatic compounds by a strain of Pseudomonas putida. 7,8-dihydroxykynurenate 8,8a-dioxygenase 7,8-dihydroxykynurenate oxygenase Iron 7,8-dihydroxykynurenate + O(2) = 5-(3-carboxy-3-oxopropenyl)-4,6-dihydroxypyridine-2-carboxylate. Indoleamine 2,3-dioxygenase Tryptophan 2,3-dioxygenase Tryptophan peroxidase L-tryptophan pyrrolase Tryptamine 2,3-dioxygenase L-tryptophan 2,3-dioxygenase Tryptophan oxygenase Indolamine 2,3-dioxygenase Tryptamin 2,3-dioxygenase Tryptophanase Tryptophan pyrrolase Specific for tryptophan as substrate, but is far more active with L-tryptophan than with D-tryptophan. Catalyzes, together with EC 1.13.11.52, the first and rate-limiting step in the kynurenine pathway, the major pathway of tryptophan metabolism. L-tryptophan + O(2) = N-formyl-L-kynurenine. Heme Lipoxygenase Lipoperoxidase Carotene oxidase Lipoxidase Also oxidizes other methylene-interrupted polyunsaturated fatty acids. Iron Linoleate + O(2) = (9Z,11E)-(13S)-13-hydroperoxyoctadeca-9,11-dienoate. Ascorbate 2,3-dioxygenase Ascorbate + O(2) + H(2)O = oxalate + threonate. Iron 2,3-dihydroxybenzoate 3,4-dioxygenase o-pyrocatechuate oxygenase 2,3-dihydroxybenzoic oxygenase 2,3-dihydroxybenzoate + O(2) = 3-carboxy-2-hydroxymuconate semialdehyde. 3,4-dihydroxyphenylacetate 2,3-dioxygenase HPC dioxygenase Homoprotocatechuate 2,3-dioxygenase 3,4-dihydroxyphenylacetate + O(2) = 2-hydroxy-5-carboxymethylmuconate semialdehyde. Iron 3-carboxyethylcatechol 2,3-dioxygenase Iron 3-(2,3-dihydroxyphenyl)propanoate + O(2) = 2-hydroxy-6-oxonona-2,4-diene-1,9-dioate. Indole oxidase Indole 2,3-dioxygenase Flavoprotein A second enzyme from Tecoma stans, which is not a flavoprotein, uses four atoms of oxygen and forms anthranilate as the final product. Copper One enzyme from Tecoma stans is also a flavoprotein containing copper and uses three atoms of oxygen per molecule of indole, to form anthranil (3,4-benzisoxazole). The enzyme from Jasminum is a flavoprotein containing copper, and forms anthranilate as the final product. Indole + O(2) = 2-formylaminobenzaldehyde. Sulfur dioxygenase Sulfur oxygenase Glutathione (GSH) plays a catalytic role in elemental sulfur activation, but is not consumed during the enzymic reaction. The sulfite can be further converted into sulfate, thiosulfate or S-sulfoglutathione (GSSO(3)(-)) non-enzymically. Iron GSH and elemental sulfur react non-enzymically to yield S-sulfanylglutathione and it is only in this form that the sulfur can be oxidized to yield sulfite. Sulfur + O(2) + H(2)O = sulfite + 2 H(+). Cysteamine oxygenase Cysteamine dioxygenase Persulfurase 3-aminopropanethiol (homocysteamine) and 2-mercaptoethanol can also act as substrates, but glutathione, cysteine, and cysteine ethyl-and methyl esters are not good substrates. 2-aminoethanethiol + O(2) = hypotaurine. Involved in the biosynthesis of taurine. Requires catalytic amounts of a cofactor-like compound, such as sulfur, sufide, selenium or methylene blue for maximal activity. Iron 2,3-pyrocatechase Catechol 2,3-dioxygenase Metapyrocatechase Cato2ase Catechol + O(2) = 2-hydroxymuconate semialdehyde. The enzyme from Alcaligenes sp. strain O-1 has also been shown to catalyze the reaction: 2,3-dihydroxybenzenesulfonate + O(2) + H(2)O = 2-hydroxymuconate + bisulfite and has been referred to as 2,3-dihydroxybenzenesulfonate 2,3-dioxygenase. Further work will be necessary to show whether or not this is a distinct enzyme. Iron Cysteine dioxygenase Iron NAD(P)H L-cysteine + O(2) = 3-sulfinoalanine. Caffeate 3,4-dioxygenase 3,4-dihydroxy-trans-cinnamate + O(2) = 3-(2-carboxyethenyl)-cis,cis-muconate. 2,3-dihydroxyindole 2,3-dioxygenase 2,3-dihydroxyindole + O(2) + H(+) = anthranilate + CO(2). Quercetin 2,3-dioxygenase Copper or iron Quercetin + O(2) = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H(+). Quercetin is a flavonol (5,7,3',4'-tetrahydroxyflavonol). Steroid 4,5-dioxygenase 3-alkylcatechol 2,3-dioxygenase 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione 4,5-dioxygenase Also acts on 3-isopropylcatechol and 3-tert-butyl-5-methylcatechol. Iron 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + O(2) = 3-hydroxy-5,9,17-trioxo-4,5:9,10-disecoandrosta-1(10),2-dien-4-oate. Pyrrolooxygenase Tryptophan pyrrolooxygenase Peptide-tryptophan 2,3-dioxygenase Also acts on tryptophan. Peptide tryptophan + O(2) = peptide formylkynurenine. 4-hydroxyphenylpyruvate hydroxylase p-hydroxyphenylpyruvate oxidase 4-hydroxyphenylpyruvate dioxygenase p-hydroxyphenylpyruvate dioxygenase 4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2). http://purl.uniprot.org/mim/140350 http://purl.uniprot.org/mim/276710 Iron 2,3-dihydroxybenzoate 2,3-dioxygenase Also acts, more slowly, with 2,3-dihydroxy-4-methylbenzoate and 2,3-dihydroxy-4-isopropylbenzoate. 2,3-dihydroxybenzoate + O(2) = 2-carboxy-cis,cis-muconate. Stizolobate synthase Zinc The intermediate product undergoes ring closure and oxidation, with NAD(P)(+) as acceptor, to stizolobic acid. 3,4-dihydroxy-L-phenylalanine + O(2) = 4-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde. Protocatechuate 3,4-dioxygenase Protocatechuate oxygenase Iron 3,4-dihydroxybenzoate + O(2) = 3-carboxy-cis,cis-muconate. Stizolobinate synthase 3,4-dihydroxy-L-phenylalanine + O(2) = 5-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde. The intermediate product undergoes ring closure and oxidation, with NAD(P)(+) as acceptor, to stizolobinic acid. Zinc Arachidonate 12-lipoxygenase 12-lipoxygenase The product is rapidly reduced to the corresponding 12S-hydroxy compound. Iron Arachidonate + O(2) = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. 2-nitropropane dioxygenase 2-NPD Nitroalkane oxidase 2 2-nitropropane + O(2) = 2 acetone + 2 nitrite. While the enzyme from the fungus Neurospora crassa contains non-covalently bound FMN as the cofactor, that from the yeast Williopsis mrakii contains FAD. FAD or FMN Some other nitroalkanes, including nitroethane, 1-nitropropane and 3-nitropentan-2-ol, can act as donors, but more slowly. Has broad substrate specificity that is independent of substrate size. Differs from EC 1.7.3.1 in that the preferred substrates are anionic nitronates rather than neutral nitroalkanes. 15-lipoxygenase Arachidonate 15-lipoxygenase Arachidonate omega(6) lipoxygenase The product is rapidly converted to the corresponding 15S-hydroxy compound. Arachidonate + O(2) = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate. Iron 5-lipoxygenase Arachidonic 5-lipoxygenase Leukotriene-A(4) synthase Delta(5)-lipoxygenase Arachidonic acid 5-lipoxygenase 5-Delta-lipoxygenase C-5-lipoxygenase Arachidonate 5-lipoxygenase LTA synthase Iron (1) Arachidonate + O(2) = (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoate. (2) (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoate = (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H(2)O. The product of the second reaction, (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate, is leukotriene A(4). Pyrogallol 1,2-oxygenase 1,2,3-trihydroxybenzene + O(2) = (Z)-5-oxohex-2-enedioate. Chloridazon-catechol dioxygenase 5-amino-4-chloro-2-(2,3-dihydroxyphenyl)-3(2H)-pyridazinone + O(2) = 5-amino-4-chloro-2-(2-hydroxymuconoyl)-3(2H)-pyridazinone. Not identical with EC 1.13.11.1, EC 1.13.11.2 or EC 1.13.11.5. Iron Involved in the breakdown of the herbicide chloridazon. Hydroxyquinol 1,2-dioxygenase The product isomerizes to 2-maleylacetate (cis-hexenedioate). Highly specific; catechol and pyrogallol are acted on at less than 1% of the rate at which hydroxyquinol is oxidized. Benzene-1,2,4-triol + O(2) = 3-hydroxy-cis,cis-muconate. Iron 1-hydroxy-2-naphthoate 1,2-dioxygenase 1-hydroxy-2-naphthoic acid dioxygenase 1-hydroxy-2-naphthoate-degrading enzyme Involved, with EC 4.1.2.34, in the metabolism of phenanthrene in bacteria. 1-hydroxy-2-naphthoate + O(2) = (3Z)-4-(2-carboxyphenyl)-2-oxobut-3-enoate. Iron 2,3-dihydroxybiphenyl dioxygenase Biphenyl-2,3-diol 1,2-dioxygenase Biphenyl-2,3-diol + O(2) = 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate + H(2)O. Not identical with EC 1.13.11.2. Also acts on 3-isopropylcatechol, forming 7-methyl-2-hydroxy-6-oxo-octa-2,4-dienoate. Gentisate 1,2-dioxygenase Gentisate oxygenase Gentisic acid oxidase Iron 2,5-dihydroxybenzoate + O(2) = maleylpyruvate. 8-lipoxygenase Arachidonate 8-lipoxygenase Arachidonate + O(2) = (5Z,9E,11Z,14Z)-(8R)-8-hydroperoxyicosa-5,9,11,14-tetraenoate. An enzyme from the coral Pseudoplexaura porosa. Iron 2,4'-dihydroxyacetophenone dioxygenase 2,4'-dihydroxyacetophenone + O(2) = 4-hydroxybenzoate + formate. Lignostilbene alpha-beta-dioxygenase The enzyme catalyzes oxidative cleavage of the interphenyl double bond in the synthetic substrate and lignin-derived stilbenes. Iron It is responsible for the degradation of a diarylpropane-type structure in lignin. 1,2-bis(4-hydroxy-3-methoxyphenyl)ethylene + O(2) = 2 vanillin. Linoleate (8R)-dioxygenase Linoleate diol synthase Linoleate 8-dioxygenase Heme Linoleate + O(2) = (9Z,12Z)-(7S,8S)-dihydroxyoctadeca-9,12-dienoate. Oleate and linolenate are also substrates, whereas stearate, elaidate, gamma-linolenate, arachidonate and eicosapentaenate are not. This enzyme differs from EC 1.13.11.12 because it catalyzes the formation of a hydroperoxide without affecting the double bonds of the substrate. Manganese lipoxygenase Linoleate 11-lipoxygenase Linoleate dioxygenase Linoleate + O(2) = (9Z,12Z)-(11S)-11-hydroperoxyoctadeca-9,12-dienoate. It also acts on alpha-linolenate, whereas gamma-linolenate is a poor substrate. Oleate and arachidonate are not substrates. The product (9Z,12Z)-(11S)-11-hydroperoxyoctadeca-9,12-dienoate, is converted, more slowly, into (9Z,11E)-(13R)-13-hydroperoxyoctadeca-9,11-dienoate. The enzyme from the fungus Gaeumannomyces graminis requires Mn(2+). 4-hydroxyphenylpyruvate dioxygenase II 4-hydroxymandelate synthase Involved in the biosynthesis of the vancomycin group of glycopeptide antibiotics. 4-hydroxyphenylpyruvate + O(2) = 4-hydroxymandelate + CO(2). Iron Quinoline-3,4-diol 2,4-dioxygenase (1H)-3-hydroxy-4-oxoquinoline 2,4-dioxygenase 3-hydroxy-4-oxoquinoline 2,4-dioxygenase 3-hydroxy-4-oxo-1,4-dihydroquinoline 2,4-dioxygenase 3-hydroxy-4(1H)-one, 2,4-dioxygenase The enzyme from Pseudomonas putida is highly specific for this substrate. 3-hydroxy-1H-quinolin-4-one + O(2) = N-formylanthranilate + CO. Fission of two C-C bonds: 2,4-dioxygenolytic cleavage with concomitant release of carbon monoxide. Does not contain a metal center or organic cofactor. (1H)-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase 3-hydroxy-2-methylquinolin-4-one 2,4-dioxygenase The enzyme from Arthrobacter sp. can also act on 3-hydroxy-4-oxoquinoline, forming N-formylanthranilate and CO (cf. EC 1.13.11.47), but more slowly. Fission of two C-C bonds: 2,4-dioxygenolytic cleavage with concomitant release of carbon monoxide. Does not contain a metal center or organic cofactor. 3-hydroxy-2-methyl-1H-quinolin-4-one + O(2) = N-acetylanthranilate + CO. Chlorite dismutase Chlorite O(2)-lyase Reaction occurs in the reverse direction in chlorate-and perchlorate-reducing bacteria. Chloride + O(2) = chlorite. There is no activity when chlorite is replaced by hydrogen peroxide, perchlorate, chlorate or nitrite. The term 'chlorite dismutase' is misleading as the reaction does not involve dismutation/disproportionation. Iron Protoheme IX Homogentisate 1,2-dioxygenase Homogentisicase Homogentisate oxygenase Homogentisic acid oxidase Homogentisate + O(2) = 4-maleylacetoacetate. Iron http://purl.uniprot.org/mim/203500 Diketone cleaving enzyme Diketone cleaving dioxygenase Acetylacetone dioxygenase Acetylacetone-cleaving enzyme Forms the first step in the acetylacetone degradation pathway of Acinetobacter johnsonii. Iron While acetylacetone is by far the best substrate, heptane-3,5-dione, octane-2,4-dione, 2-acetylcyclohexanone and ethyl acetoacetate can also act as substrates. Pentane-2,4-dione + O(2) = acetate + 2-oxopropanal. VP14 Nine-cis-epoxycarotenoid dioxygenase NCED 9-cis-epoxycarotenoid dioxygenase (1) A 9-cis-epoxycarotenoid + O(2) = 2-cis,4-trans-xanthoxin + a 12'-apo-carotenal. In vitro, it will cleave 9-cis-zeaxanthin. (3) 9'-cis-neoxanthin + O(2) = 2-cis,4-trans-xanthoxin + (3S,5R,6R)-5,6-dihydroxy-6,7-didehydro-5,6-dihydro-12'-apo-beta-caroten-12'-al. (2) 9-cis-violaxanthin + O(2) = 2-cis,4-trans-xanthoxin + (3S,5R,6S)-5,6-epoxy-3-hydroxy-5,6-dihydro-12'-apo-beta-caroten-12'-al. Acts on 9-cis-violaxanthin and 9'-cis-neoxanthin but not on the all-trans isomers. Iron The other enzymes involved in the abscisic-acid biosynthesis pathway are EC 1.1.1.288, EC 1.2.3.14 and EC 1.14.13.93. Catalyzes the first step of abscisic-acid biosynthesis from carotenoids in chloroplasts, in response to water stress. IDO Tryptophan pyrrolase Indoleamine 2,3-dioxygenase Heme (2) L-tryptophan + O(2) = N-formyl-L-kynurenine. Has broader substrate specificity than EC 1.13.11.11. While the enzyme is more active with D-tryptophan than L-tryptophan, its only known function to date is in the metabolism of L-tryptophan. Superoxide radicals can replace O(2) as oxygen donor. (1) D-tryptophan + O(2) = N-formyl-D-kynurenine. Requires ascorbic acid and methylene blue for activity. Is induced in response to pathological conditions and host-defense mechanisms. E-2 Acireductone dioxygenase 2-hydroxy-3-keto-5-thiomethylpent-1-ene dioxygenase ARD Acireductone dioxygenase (Ni(2+)-requiring) The enzyme from Klebsiella oxytoca (formerly Klebsiella pneumoniae) ATCC 8724 is involved in the methionine salvage pathway. Nickel If Fe(2+) is bound instead of Ni(2+), the reaction catalyzed by EC 1.13.11.54 occurs instead. 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O(2) = 3-(methylthio)propanoate + formate + CO. Acireductone dioxygenase (Fe(2+)-requiring) 2-hydroxy-3-keto-5-thiomethylpent-1-ene dioxygenase E-2' ARD' Acireductone dioxygenase The enzyme from Klebsiella oxytoca (formerly Klebsiella pneumoniae) ATCC 8724 is involved in the methionine salvage pathway. Iron(2+) 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O(2) = 4-(methylthio)-2-oxobutanoate + formate. If Ni(2+) is bound instead of Fe(2+), the reaction catalyzed by EC 1.13.11.53 occurs instead. Sulfur oxygenase Sulfur oxygenase/reductase Sulfur oxygenase reductase Another reaction product is thiosulfate, but this is probably formed non-enzymically at elevated temperature from sulfite and sulfur. 4 sulfur + 4 H(2)O + O(2) = 2 H(2)S + 2 HSO(3)(-) + 2 H(+). This enzyme differs from EC 1.13.11.18 and EC 1.97.1.3 in that both activities are found together. Elemental sulfur is both the electron donor and one of the two known acceptors, the other being oxygen. Iron 3-hydroxyanthranilic acid oxidase 3-hydroxyanthranilic acid dioxygenase 3-hydroxyanthranilate 3,4-dioxygenase 3-hydroxyanthranilate oxygenase Iron The product of the reaction spontaneously rearrange to quinolinic acid (quin). 3-hydroxyanthranilate + O(2) = 2-amino-3-carboxymuconate semialdehyde. Protocatechuate 4,5-oxygenase Protocatechuate 4,5-dioxygenase Iron Protocatechuate + O(2) = 4-carboxy-2-hydroxymuconate semialdehyde. 2,5-dihydroxypyridine 5,6-dioxygenase Pyridine-2,5-diol dioxygenase 2,5-dihydroxypyridine oxygenase 2,5-dihydroxypyridine + O(2) + H(2)O = maleamate + formate. Iron With incorporation of one atom of oxygen Arginine 2-monooxygenase Arginine decarboxylase Arginine decarboxy-oxidase Arginine oxygenase (decarboxylating) L-arginine + O(2) = 4-guanidinobutanamide + CO(2) + H(2)O. Flavoprotein Also acts on canavanine and homoarginine. Apo-beta-carotenoid-14',13'-dioxygenase Unlike EC 1.14.99.36, it is not active toward beta-carotene. A thiol-dependent enzyme. 8'-apo-beta-carotenol + O(2) = 14'-apo-beta-carotenal + H(2)O. Presumably 2-methyl-6-oxohepta-2,4-dienal is also formed in this reaction. Oplophorus luciferase Oplophorus-luciferin 2-monooxygenase Oplophorus luciferin + O(2) = oxidized Oplophorus luciferin + CO(2) + light. The luciferase from the deep sea shrimp Oplophorus gracilorostris is a complex composed of more than one protein. The enzyme's specificity is quite broad, with both coelenterazine and bisdeoxycoelenterazine being good substrates. CAO Cholorophyll-b synthase Chlorophyllide a oxygenase Chlorophyllide-a oxygenase (1) Chlorophyllide a + O(2) + NADPH = 7-hydroxychlorophyllide a + H(2)O + NADP(+). (2) 7-hydroxychlorophyllide a + O(2) + NADPH = chlorophyllide b + 2 H(2)O + NADP(+). Catalyzes two successive hydroxylations at the 7-methyl group of chlorophyllide a. Iron The second step yields the aldehyde hydrate, which loses H(2)O spontaneously to form chlorophyllide b. Chlorophyll a and protochlorophyllide a are not substrates. Lysine oxygenase Lysine 2-monooxygenase FAD Also acts on other diamino acids. L-lysine + O(2) = 5-aminopentanamide + CO(2) + H(2)O. Tryptophan 2-monooxygenase L-tryptophan + O(2) = (indol-3-yl)acetamide + CO(2) + H(2)O. Lactate oxidase Lactate 2-monooxygenase Lactate oxygenase Lactate oxidative decarboxylase FMN (S)-lactate + O(2) = acetate + CO(2) + H(2)O. Renilla-luciferin 2-monooxygenase Aequorin Renilla-type luciferase Luciferase In vitro, Renilla luciferase emits blue light in the absence of any green fluorescent protein. In vivo, the excited state luciferin--luciferase complex undergoes the process of nonradiative energy transfer to an accessory protein, Renilla green fluorescent protein, which results in green bioluminescence. From the soft coral coelenterate Renilla reniformis. The luciferin is bound to a luciferin-binding protein (BP-LH2). The bioluminescent reaction between the luciferin complex, luciferase and oxygen is triggered by calcium ions. Renilla luciferin + O(2) = oxidized Renilla luciferin + CO(2) + light. Cypridina-type luciferase Cypridina-luciferin 2-monooxygenase Luciferase The enzyme may be assayed by measurement of light emission. Cypridina luciferin is (3-(3,7-dihydro-6-(1H-indol-3-yl)-2-((S)-1-methyl-6-propyl)-3-oxoimidazo-[1,2-a]pyrazin-8-yl)propyl)guanidine. Cypridina luciferin + O(2) = oxidized Cypridina luciferin + CO(2) + light. Luciferase Firefly luciferase Photinus pyralis luciferase Photinus-luciferin 4-monooxygenase (ATP-hydrolyzing) The first step in the reaction is the formation of an acid anhydride between the carboxylic group and AMP, with the release of diphosphate. Photinus luciferin + O(2) + ATP = oxidized Photinus luciferin + CO(2) + AMP + diphosphate + light. The enzyme may be assayed by measurement of light emission. Photinus luciferin is (S)-4,5-dihydro-2-(6-hydroxy-2-benzo-thiazoloyl)-4-thiazolecarboxylic acid. Watasenia-type luciferase Watasenia-luciferin 2-monooxygenase Luciferase The enzyme may be assayed by measurement of light emission. Watasenia luciferin + O(2) = oxidized Watasenia luciferin + CO(2) + light. Watasenia luciferin is 8-(phenylmethyl)-6-(4-sulfooxyphenyl)-2-((4-sulfooxyphenyl)methyl)imidazo[1,2-a]pyrazin-3(7H)-one. L-phenylalanine oxidase (deaminating and decarboxylating) Phenylalanine 2-monooxygenase Phenylalanine (deaminating, decarboxylating) oxidase The reaction shown above is about 80% of the reaction catalyzed; the remaining 20% is: L-phenylalanine + O(2) + H(2)O = 3-phenylpyruvic acid + NH(3) + H(2)O(2), a reaction similar to that of EC 1.4.3.2. L-phenylalanine + O(2) = 2-phenylacetamide + CO(2) + H(2)O. Miscellaneous (requires further characterization) Inositol oxygenase Myo-inositol oxygenase MOO Meso-inositol oxygenase Myo-inositol + O(2) = D-glucuronate + H(2)O. Iron Tryptophan 2'-dioxygenase Indole-3-alkane alpha-hydroxylase Tryptophan side-chain alpha,beta-oxidase TSO Tryptophan side-chain oxidase Best substrates are L-tryptophan and 5-hydroxy-L-tryptophan. Acts on a number of indole-3-alkane derivatives, oxidizing the 3-side-chain in the 2'-position. L-tryptophan + O(2) = (indol-3-yl)glycolaldehyde + CO(2) + NH(3). Heme Acting on paired donors, with incorporation or reduction of molecular oxygen With 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors Gamma-butyrobetaine hydroxylase Gamma-butyrobetaine,2-oxoglutarate dioxygenase Gamma-butyrobetaine dioxygenase Gamma-BBH Ascorbate 4-trimethylammoniobutanoate + 2-oxoglutarate + O(2) = 3-hydroxy-4-trimethylammoniobutanoate + succinate + CO(2). Iron Deoxyuridine-uridine 1'-dioxygenase Pyrimidine-deoxynucleoside 1'-dioxygenase Pyrimidine-deoxynucleoside,2-oxoglutarate 1'-dioxygenase Ascorbate Cf. EC 1.14.11.3. 2'-deoxyuridine + 2-oxoglutarate + O(2) = uracil + 2-deoxyribonolactone + succinate + CO(2). Iron Hyoscyamine (6S)-hydroxylase Hyoscyamine 6-beta-hydroxylase Hyoscyamine (6S)-dioxygenase Iron Ascorbate L-hyoscyamine + 2-oxoglutarate + O(2) = (6S)-hydroxyhyoscyamine + succinate + CO(2). Gibberellin-44 dioxygenase Gibberellin A44 oxidase Iron Gibberellin 44 + 2-oxoglutarate + O(2) = gibberellin 19 + succinate + CO(2). Gibberellin 2-beta-dioxygenase Gibberellin 2-beta-hydroxylase Also acts on a number of other gibberellins. Iron Gibberellin 1 + 2-oxoglutarate + O(2) = 2-beta-hydroxygibberellin 1 + succinate + CO(2). Hydroxyhyoscyamine dioxygenase 6-beta-hydroxyhyoscyamine epoxidase (6S)-6-hydroxyhyoscyamine + 2-oxoglutarate + O(2) = scopolamine + succinate + CO(2). Iron Ascorbate Gibberellin 3-beta-hydroxylase Gibberellin 3-beta-dioxygenase Iron Gibberellin 20 + 2-oxoglutarate + O(2) = gibberellin 1 + succinate + CO(2). Ascorbate Aspartate beta-hydroxylase Peptide-aspartate beta-dioxygenase Aspartyl/asparaginyl beta-hydroxylase Peptide L-aspartate + 2-oxoglutarate + O(2) = peptide 3-hydroxy-L-aspartate + succinate + CO(2). Some vitamin K-dependent coagulation factors, as well as synthetic peptides based on the structure of the first epidermal growth factor domain of human coagulation factor IX or X, can act as acceptors. Iron Taurine dioxygenase Alpha-ketoglutarate-dependent taurine dioxygenase 2-aminoethanesulfonate dioxygenase The enzyme from Escherichia coli also acts on pentanesulfonate, 3-(N-morpholino)propanesulfonate and 2-(1,3-dioxoisoindolin-2-yl)ethanesulfonate, but at lower rates. Iron Ascorbate Taurine + 2-oxoglutarate + O(2) = sulfite + aminoacetaldehyde + succinate + CO(2). Phytanoyl-CoA alpha-hydroxylase Phytanoyl-CoA 2-hydroxylase Phytanoyl-CoA 2 oxoglutarate dioxygenase Phytanoyl-CoA dioxygenase Phytanoyl-CoA hydroxylase Iron Phytanoyl-CoA + 2-oxoglutarate + O(2) = 2-hydroxyphytanoyl-CoA + succinate + CO(2). Part of the peroxisomal phytanic acid alpha-oxidation pathway. http://purl.uniprot.org/mim/266500 Ascorbate Anthocyanidin synthase Leucoanthocyanidin dioxygenase Leucocyanidin oxygenase Involved in the pathway by which many flowering plants make anthocyanin (glycosylated anthocyandin) flower pigments. Ascorbate Acidification of the products gives anthocyanidin, which, however, may not be a natural precursor of the anthocyanins. Iron The intermediates are transformed into cis-and trans-dihydroquercetin, which the enzyme can also oxidize to quercetin. Leucocyanidin + 2-oxoglutarate + O(2) = cis- and trans-dihydroquercetins + succinate + CO(2). Protocollagen hydroxylase Proline,2-oxoglutarate 4-dioxygenase Prolyl hydroxylase Procollagen-proline dioxygenase Procollagen-proline,2-oxoglutarate-4-dioxygenase Prolyl 4-hydroxylase Procollagen-proline 4-dioxygenase Proline hydroxylase Ascorbate Procollagen L-proline + 2-oxoglutarate + O(2) = procollagen trans-4-hydroxy-L-proline + succinate + CO(2). Iron D17H Desacetoxyvindoline 4-hydroxylase Desacetoxyvindoline-4-hydroxylase Desacetyoxyvindoline-17-hydroxylase Desacetoxyvindoline,2-oxoglutarate:oxygen oxidoreductase (4-beta-hydroxylating) Iron Ascorbate Also acts on 3-hydroxy-16-methoxy-2,3-dihydrotabersonine and to a lesser extent on 16-methoxy-2,3-dihydrotabersonine. Desacetoxyvindoline + 2-oxoglutarate + O(2) = desacetylvindoline + succinate + CO(2). Clavaminate synthase Clavaminic acid synthase Iron (2) Proclavaminate + 2-oxoglutarate + O(2) = dihydroclavaminate + succinate + CO(2) + 2 H(2)O. Catalyzes three separate oxidative reactions in the pathway for the biosythesis of the beta-lactamase inhibitor clavulanate in Streptomyces clavuligerus. (1) Deoxyamidinoproclavaminate + 2-oxoglutarate + O(2) = amidinoproclavaminate + succinate + CO(2) + H(2)O. The three reactions are all catalyzed at the same nonheme iron site. The first step (hydroxylation) is separated from the latter two (oxidative cyclization and desaturation) by the action of EC 3.5.3.22. (3) Dihydroclavaminate + 2-oxoglutarate + O(2) = clavaminate + succinate + CO(2) + 2 H(2)O. FNS I Flavone synthase I Flavone synthase Iron Ascorbate A flavanone + 2-oxoglutarate + O(2) = a flavone + succinate + CO(2) + H(2)O. FLS Flavonoid 2-oxoglutarate-dependent dioxygenase Flavonol synthase A dihydroflavonol + 2-oxoglutarate + O(2) = a flavonol + succinate + CO(2) + H(2)O. In addition to the desaturation of (2R,3R)-dihydroflavonols to flavonols, the enzyme from the satsuma Citrus unshiu also has a non-specific activity that trans-hydroxylates the flavanones (2S)-naringenin and the unnatural (2R)-naringenin at C-3 to kaempferol and (2R,3R)-dihydrokaempferol, respectively. Iron IDS3 2'-deoxymugineic-acid 2'-dioxygenase Iron It is also likely that this enzyme can catalyze the hydroxylation of 3-epihydroxy-2'-deoxymugineic acid to form 3-epihydroxymugineic acid. 2'-deoxymugineic acid + 2-oxoglutarate + O(2) = mugineic acid + succinate + CO(2). Mugineic-acid 3-dioxygenase IDS2 (2) 2'-deoxymugineic acid + 2-oxoglutarate + O(2) = 3-epihydroxy-2'-deoxymugineic acid + succinate + CO(2). Iron(2+) (1) Mugineic acid + 2-oxoglutarate + O(2) = 3-epihydroxymugineic acid + succinate + CO(2). Deacetoxycephalosporin C hydroxylase DAOC hydroxylase 3'-methylcephem hydroxylase DACS Deacetoxycephalosporin-C hydroxylase Deacetylcephalosporin C synthase Iron The enzyme can also use 3-exomethylenecephalosporin C as a substrate to form deacetoxycephalosporin C, although more slowly. In Acremonium chrysogenum, the enzyme forms part of a bifunctional protein along with EC 1.14.20.1. It is a separate enzyme in Streptomyces clavuligerus. Deacetoxycephalosporin C + 2-oxoglutarate + O(2) = deacetylcephalosporin C + succinate + CO(2). H3-K36-specific demethylase JmjC domain-containing histone demethylase 1A Histone demethylase [Histone H3]-lysine-36 demethylase Histone-lysine (H3-K36) demethylase JHDM1A Of the seven potential methylation sites in histones H3 (K4, K9, K27, K36, K79) and H4 (K20, R3) from HeLa cells, the enzyme is specific for Lys-36. Lysine residues exist in three methylation states (mono-, di-and trimethylated). It can also demethylate the monomethyl-but not the trimethyl form of Lys-36. The enzyme preferentially demethylates the dimethyl form of Lys-36 (K36me2), which is its natural substrate, to form the monomethyl and unmethylated forms of Lys-36. (1) Protein N(6),N(6)-dimethyl-L-lysine + 2-oxoglutarate + O(2) = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO(2). (2) Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O(2) = protein L-lysine + succinate + formaldehyde + CO(2). Iron(2+) P-3-H Proline 3-hydroxylase The enzyme is specific for L-proline as D-proline, trans-4-hydroxy-L-proline, cis-4-hydroxy-L-proline and 3,4-dehydro-DL-proline are not substrates. Unlike the proline hydroxylases involved in collagen biosynthesis (EC 1.14.11.2 and EC 1.14.11.7), this enzyme does not require ascorbate for activity although it does increase the activity of the enzyme. L-proline + 2-oxoglutarate + O(2) = cis-3-hydroxy-L-proline + succinate + CO(2). Iron(2+) Thymidine 2-oxoglutarate dioxygenase Deoxyuridine 2'-dioxygenase Thymidine dioxygenase Thymidine 2'-dioxygenase Thymidine 2'-hydroxylase Pyrimidine-deoxynucleoside 2'-dioxygenase Pyrimidine-deoxynucleoside,2-oxoglutarate 2'-dioxygenase Deoxyuridine 2'-hydroxylase Pyrimidine deoxyribonucleoside 2'-hydroxylase 2'-deoxyuridine + 2-oxoglutarate + O(2) = uridine + succinate + CO(2). Iron Also acts on thymidine (cf. EC 1.14.11.10). Ascorbate Procollagen-lysine 5-dioxygenase Lysine hydroxylase Lysine,2-oxoglutarate 5-dioxygenase Procollagen-lysine,2-oxoglutarate 5-dioxygenase Lysyl hydroxylase Ascorbate http://purl.uniprot.org/mim/609220 Iron http://purl.uniprot.org/mim/225400 Procollagen L-lysine + 2-oxoglutarate + O(2) = procollagen 5-hydroxy-L-lysine + succinate + CO(2). Thymine dioxygenase Thymine,2-oxoglutarate dioxygenase Thymine 7-hydroxylase Also acts on 5-hydroxymethyluracil to oxidize its -CH(2)-OH group first to -CHO and then to -COOH. Ascorbate Iron Thymine + 2-oxoglutarate + O(2) = 5-hydroxymethyluracil + succinate + CO(2). Prolyl 3-hydroxylase Proline,2-oxoglutarate 3-dioxygenase Procollagen-proline 3-dioxygenase Procollagen-proline,2-oxoglutarate 3-dioxygenase Procollagen L-proline + 2-oxoglutarate + O(2) = procollagen trans-3-hydroxy-L-proline + succinate + CO(2). Iron Ascorbate TML-alpha-ketoglutarate dioxygenase TML hydroxylase Epsilon-trimethyllysine 2-oxoglutarate dioxygenase Trimethyllysine alpha-ketoglutarate dioxygenase Trimethyllysine dioxygenase TMLD Trimethyllysine,2-oxoglutarate dioxygenase TML dioxygenase Iron(2+) Ascorbate N(6),N(6),N(6)-trimethyl-L-lysine + 2-oxoglutarate + O(2) = 3-hydroxy-N(6),N(6),N(6)-trimethyl-L-lysine + succinate + CO(2). Flavanone synthase I Flavanone 3-beta-hydroxylase Naringenin 3-dioxygenase Naringenin,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating) Flavanone 3-hydroxylase Naringenin 3-hydroxylase (2S)-flavanone 3-hydroxylase Flavanone 3-dioxygenase Iron Ascorbate A flavanone + 2-oxoglutarate + O(2) = a dihydroflavonol + succinate + CO(2). With NADH or NADPH as one donor, and incorporation of two atoms of oxygen into one donor Anthranilate 1,2-dioxygenase (deaminating, decarboxylating) Anthranilate hydroxylase Anthranilic acid hydroxylase Anthranilic hydroxylase Iron Anthranilate + NAD(P)H + O(2) = catechol + CO(2) + NAD(P)(+) + NH(3). Benzoate hydroxylase Benzoic hydroxylase Benzoate 1,2-dioxygenase A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), and an iron-sulfur oxygenase. Benzoate + NADH + O(2) = 1,2-dihydroxycyclohexa-3,5-diene-1-carboxylate + NAD(+). Iron Toluene dioxygenase Toluene 1,2-dioxygenase A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), an iron-sulfur oxygenase, and a ferredoxin. Some other aromatic compounds, including ethylbenzene, 4-xylene and some halogenated toluenes, are converted into the corresponding cis-dihydrodiols. Toluene + NADH + O(2) = (1S,2R)-3-methylcyclohexa-3,5-diene-1,2-diol + NAD(+). Naphthalene 1,2-dioxygenase A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), an iron-sulfur oxygenase, and ferredoxin. Naphthalene + NADH + O(2) = (1R,2S)-1,2-dihydronaphthalene-1,2-diol + NAD(+). Iron 2-chlorobenzoate 1,2-dioxygenase 2-chlorobenzoate + NADH + O(2) = catechol + chloride + NAD(+) + CO(2). Iron 2-aminosulfobenzene 2,3-dioxygenase 2-aminobenzenesulfonate 2,3-dioxygenase 2-aminobenzenesulfonate + NADH + O(2) = 2,3-dihydroxybenzenesulfonate + NH(3) + NAD(+). 1,4-dicarboxybenzoate 1,2-dioxygenase Terephthalate 1,2-dioxygenase Benzene-1,4-dicarboxylate 1,2-dioxygenase Terephthalate + NADH + O(2) = (1R,6S)-dihydroxycyclohexa-2,4-diene-1,4-dicarboxylate + NAD(+). In Comamonas testoteroni, contains a Rieske [2Fe-2S] center. 2-hydroxyquinoline 5,6-dioxygenase Quinolin-2-ol 5,6-dioxygenase 2-oxo-1,2-dihydroquinoline 5,6-dioxygenase Quinolin-2(1H)-one 5,6-dioxygenase Quinolin-2-ols exist largely as their quinolin-2(1H)-one tautomers. Quinolin-2-ol + NADH + O(2) = 2,5,6-trihydroxy-5,6-dihydroquinoline + NAD(+). 3-methylquinolin-2-ol, quinolin-8-ol and quinolin-2,8-diol are also substrates. Nitric oxide dioxygenase NOD Heme 2 NO + 2 O(2) + NAD(P)H = 2 NO(3)(-) + NAD(P)(+). FAD It has been proposed that FAD functions as the electron carrier from NADPH to the ferric heme prosthetic group. Biphenyl 2,3-dioxygenase Biphenyl dioxygenase The enzyme from Burkholderia fungorum strain LB400 (previously Pseudomonas sp.) is part of a multicomponent system composed of an NADH:ferredoxin oxidoreductase (FAD cofactor), a [2Fe-2S] Rieske-type ferredoxin, and a terminal oxygenase that contains a [2Fe-2S] Rieske-type iron-sulfur cluster and a catalytic mononuclear nonheme iron center. Chlorine-substituted biphenyls can also act as substrates. Similar to the three-component enzyme systems EC 1.14.12.3 and EC 1.14.12.11. Iron Biphenyl + NADH + O(2) = (1S,2R)-3-phenylcyclohexa-3,5-diene-1,2-diol + NAD(+). HcaA1A2CD 3-phenylpropanoate dioxygenase Hca dioxygenase 3-phenylpropionate dioxygenase 3-phenylpropanoate + NADH + O(2) = 3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate + NAD(+). The product, 3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate, is then converted into 3-(2,3-dihydroxyphenyl)propanoate, by a dehydrogenase, with the concomitant regeneration of NADH. Iron This enzyme catalyzes the insertion of both atoms of molecular oxygen into positions 2 and 3 of the phenyl ring of 3-phenylpropanoate. The enzyme also acts on (2E)-3-phenylprop-2-enoate (cinnamate). Benzene hydroxylase Benzene 1,2-dioxygenase FAD Iron Benzene + NADH + O(2) = cis-cyclohexa-3,5-diene-1,2-diol + NAD(+). Iron-sulfur A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), an iron-sulfur oxygenase and ferredoxin. Methylhydroxypyridinecarboxylate oxidase Methylhydroxypyridine carboxylate dioxygenase 3-hydroxy-2-methylpyridinecarboxylate dioxygenase 3-hydroxy-2-methylpyridine-5-carboxylate + NAD(P)H + O(2) = 2-(acetamidomethylene)succinate + NAD(P)(+). FAD 5-pyridoxate dioxygenase 5-pyridoxate oxidase 3-hydroxy-4-hydroxymethyl-2-methylpyridine-5-carboxylate + NADPH + O(2) = 2-(acetamidomethylene)-3-(hydroxymethyl)succinate + NADP(+). Flavoprotein Phthalate 4,5-dioxygenase PDO Phthalate dioxygenase Iron Phthalate + NADH + O(2) = cis-4,5-dihydroxycyclohexa-1(6),2-diene-1,2-dicarboxylate + NAD(+). FMN Iron-sulfur A system, containing a reductase which is an iron-sulfur flavoprotein (FMN), an iron-sulfur oxygenase, and no independent ferredoxin. 4-sulfobenzoate 3,4-dioxygenase Iron FMN Iron-sulfur A system, containing a reductase which is an iron-sulfur flavoprotein (FMN), an iron-sulfur oxygenase, and no independent ferredoxin. 4-sulfobenzoate + NADH + O(2) = 3,4-dihydroxybenzoate + sulfite + NAD(+). 4-chlorophenylacetate 3,4-dioxygenase Iron Also acts on 4-bromophenyl acetate. A system, containing a reductase and an iron-sulfur oxygenase, and no independent ferredoxin. 4-chlorophenylacetate + NADH + O(2) = 3,4-dihydroxyphenylacetate + chloride + NAD(+). With NADH or NADPH as one donor, and incorporation of one atom of oxygen Salicylate hydroxylase Salicylic hydroxylase Salicylate 1-monooxygenase FAD Salicylate + NADH + O(2) = catechol + NAD(+) + H(2)O + CO(2). 2,6-dihydroxypyridine 3-monooxygenase Flavoprotein 2,6-dihydroxypyridine + NADH + O(2) = 2,3,6-trihydroxypyridine + NAD(+) + H(2)O. 25-hydroxycholesterol 7-alpha-monooxygenase 25-hydroxycholesterol 7-alpha-hydroxylase (1) Cholest-5-ene-3-beta,25-diol + NADPH + O(2) = cholest-5-ene-3-beta,7-alpha,25-triol + NADP(+) + H(2)O. Unlike EC 1.14.13.99 which is specific for its oxysterol substrate, this enzyme can also metabolize the oxysterols 24,25-epoxycholesterol, 22-hydroxycholesterol and 24-hydroxycholesterol, but to a lesser extent. (2) Cholest-5-ene-3-beta,27-diol + NADPH + O(2) = cholest-5-ene-3-beta,7-alpha,27-triol + NADP(+) + H(2)O. Heme-thiolate http://purl.uniprot.org/mim/603711 Senecionine N-oxygenase Senecionine monooxygenase (N-oxide-forming) Senecionine N-oxide is used by insects as a chemical defense: it is non-toxic, but it is bioactivated to a toxic form by the action of cytochrome P-450 oxidase when absorbed by insectivores. Senecionine + NADPH + O(2) = senecionine N-oxide + NADP(+) + H(2)O. While pyrrolizidine alkaloids of the senecionine and monocrotaline types are generally good substrates (e.g. senecionine, retrorsine and monocrotaline), the enzyme does not use ester alkaloids lacking an hydroxy group at C-7 (e.g. supinine and phalaenopsine), 1,2-dihydro-alkaloids (e.g. sarracine) or unesterified necine bases (e.g. senkirkine) as substrates. NADH cannot replace NADPH. Psoralen synthase Furanocoumarins protect plants from fungal invasion and herbivore attack. (+)-marmesin + NADPH + O(2) = psoralen + NADP(+) + acetone + 2 H(2)O. Specific for (+)-marmesin, and to a much lesser extent 5-hydroxymarmesin, as substrate. (+)-columbianetin, the angular furanocoumarin analog of the linear furanocoumarin (+)-marmesin, is not a substrate for the enzyme but it is a competitive inhibitor. CA4H Cinnamic acid 4-hydroxylase Cinnamate 4-monooxygenase Cinnamic acid 4-monooxygenase Cinnamate 4-hydroxylase Trans-cinnamate 4-monooxygenase Trans-cinnamate + NADPH + O(2) = 4-hydroxycinnamate + NADP(+) + H(2)O. Heme-thiolate Also acts on NADH, more slowly. p-hydroxybenzoate hydroxylase Benzoate 4-monooxygenase Benzoic acid 4-hydroxylase Benzoate-p-hydroxylase Benzoate-para-hydroxylase Benzoate 4-hydroxylase Iron Benzoate + NADPH + O(2) = 4-hydroxybenzoate + NADP(+) + H(2)O. Tetrahydropteridine 25-hydroxycholecalciferol-1-hydroxylase Calcidiol 1-monooxygenase 25-OHD-1 alpha-hydroxylase 25-hydroxycholecalciferol 1-monooxygenase 25-hydroxyvitamin D-1 alpha hydroxylase http://purl.uniprot.org/mim/264700 Calcidiol + NADPH + O(2) = calcitriol + NADP(+) + H(2)O. Heme-thiolate Trans-cinnamate 2-monooxygenase Cinnamic acid 2-hydroxylase Cinnamic 2-hydroxylase Trans-cinnamate + NADPH + O(2) = 2-hydroxycinnamate + NADP(+) + H(2)O. 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase Sterol 27-hydroxylase Cytochrome P450 27A1' Cholestanetriol 26-monooxygenase Cholesterol 27-hydroxylase Cholestanetriol 26-hydroxylase Sterol 26-hydroxylase 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol hydroxylase Heme-thiolate 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol + NADPH + O(2) = (25R)-5-beta-cholestane-3-alpha,7-alpha,12-alpha,26-tetraol + NADP(+) + H(2)O. With prolonged treatment, 26-hydroxycholesterol is converted into the corresponding 27-aldehyde and 27-oic acid. With cholesterol as well as 26-hydroxycholesterol, 24-hydroxy-and 25-hydroxycholesterol are also formed. Requires ferrodoxin. http://purl.uniprot.org/mim/213700 Acts on cholesterol, cholest-5-en-3-beta,7-alpha-diol, 7-alpha-hydroxycholest-4-en-3-one, 5-beta-cholestane-3-alpha,7-alpha-diol as well as 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Cyclopentanone monooxygenase Cyclopentanone 1,2-monooxygenase Cyclopentanone + NADPH + O(2) = 5-valerolactone + NADP(+) + H(2)O. Cholesterol 7-alpha-monooxygenase Cholesterol 7-alpha-hydroxylase Cholesterol + NADPH + O(2) = 7-alpha-hydroxycholesterol + NADP(+) + H(2)O. Heme-thiolate 4-hydroxyphenylacetic 1-hydroxylase 4-hydroxyphenylacetate 1-hydroxylase 4-hydroxyphenylacetate 1-monooxygenase 4-HPA 1-hydroxylase 4-hydroxyphenylacetate + NAD(P)H + O(2) = homogentisate + NAD(P)(+) + H(2)O. Also acts on 4-hydroxyhydratropate forming 2-methylhomogentisate and on 4-hydroxyphenoxyacetate forming hydroquinone and glycolate. FAD Taxifolin 8-monooxygenase Converts a flavanol into a flavanone. Flavoprotein Taxifolin + NAD(P)H + O(2) = 2,3-dihydrogossypetin + NAD(P)(+) + H(2)O. Also acts on fustin, but not on catechin, quercetin or mollisacacidin. 4-hydroxybenzoate 3-monooxygenase p-hydroxybenzoic acid hydroxylase p-hydroxybenzoate hydroxylase Para-hydroxybenzoate hydroxylase Most enzymes from Pseudomonas are highly specific for NAD(P)H (cf. EC 1.14.13.33). 4-hydroxybenzoate + NADPH + O(2) = protocatechuate + NADP(+) + H(2)O. FAD 2,4-dichlorophenol hydroxylase 2,4-dichlorophenol 6-monooxygenase FAD 2,4-dichlorophenol + NADPH + O(2) = 3,5-dichlorocatechol + NADP(+) + H(2)O. Also acts, more slowly, on 4-chlorophenol and 4-chloro-2-methylphenol. NADH can act instead of NADPH, but more slowly. Flavonoid 3'-monooxygenase Flavonoid 3'-hydroxylase Acts on a number of flavonoids, including naringenin and dihydrokaempferol. A flavonoid + NADPH + O(2) = a 3'-hydroxyflavonoid + NADP(+) + H(2)O. Does not act on 4-coumarate or 4-coumaroyl-CoA. Cyclohexanone oxygenase Cyclohexanone 1,2-monooxygenase Cyclohexanone:NADPH:oxygen oxidoreductase (6-hydroxylating, 1,2-lactonizing) Cyclohexanone monooxygenase In the catalytic mechanism of this enzyme, the nucleophilic species that attacks the carbonyl group is a peroxyflavin intermediate that is generated by reaction of the enzyme-bound flavin cofactor with NAD(P)H and oxygen. This enzyme is able to catalyze a wide range of oxidative reactions, including enantioselective Baeyer-Villiger reactions, sulfoxidations, amine oxidations and epoxidations. FAD Cyclohexanone + NADPH + O(2) = hexano-6-lactone + NADP(+) + H(2)O. 3-hydroxybenzoate 4-hydroxylase 3-hydroxybenzoate 4-monooxygenase 3-hydroxybenzoate + NADPH + O(2) = 3,4-dihydroxybenzoate + NADP(+) + H(2)O. FAD Also acts on a number of analogs of 3-hydroxybenzoate substituted in the 2, 4, 5 and 6 positions. 3-hydroxybenzoic acid-6-hydroxylase 3-hydroxybenzoate 6-hydroxylase 3-hydroxybenzoate 6-monooxygenase NADPH can act instead of NADH, more slowly. 3-hydroxybenzoate + NADH + O(2) = 2,5-dihydroxybenzoate + NAD(+) + H(2)O. Also acts on a number of analogs of 3-hydroxybenzoate substituted in the 2, 4, 5 and 6 positions. FAD Methane monooxygenase Methane hydroxylase Broad specificity; many alkanes can be hydroxylated, and alkenes are converted into the corresponding epoxides; CO is oxidized to CO(2), ammonia is oxidized to hydroxylamine, and some aromatic compounds and cyclic alkanes can also be hydroxylated, more slowly. Methane + NAD(P)H + O(2) = methanol + NAD(P)(+) + H(2)O. Phosphatidylcholine 12-monooxygenase Oleate Delta(12)-hydroxylase Ricinoleic acid synthase 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine + NADH + O(2) = 1-acyl-2-((S)-12-hydroxyoleoyl)-sn-glycero-3-phosphocholine + NAD(+) + H(2)O. 4-aminobenzoate hydroxylase 4-aminobenzoate dehydrogenase 4-aminobenzoate 1-monooxygenase FAD 4-aminobenzoate + NAD(P)H + O(2) = 4-hydroxyaniline + NAD(P)(+) + H(2)O + CO(2). Acts on anthranilate and 4-aminosalicylate but not on salicylate (cf. EC 1.14.13.1). 3,9-dihydroxypterocarpan 6A-monooxygenase 3,9-dihydroxypterocarpan 6A-hydroxylase (6aR,11aR)-3,9-dihydroxypterocarpan + NADPH + O(2) = (6aS,11aS)-3,6a,9-trihydroxypterocarpan + NADP(+) + H(2)O. Heme-thiolate The product of the reaction is the biosynthetic precursor of the phytoalexin glyceollin in soybean. 4-nitrophenol-2-hydroxylase 4-nitrophenol hydroxylase 4-nitrophenol 2-monooxygenase FAD 4-nitrophenol + NADH + O(2) = 4-nitrocatechol + NAD(+) + H(2)O. 4-hydroxyphenylacetic acid-3-hydroxylase 4 HPA 3-hydroxylase 4-hydroxyphenylacetate 3-monooxygenase p-hydroxyphenylacetate 3-hydroxylase 4-hydroxyphenylacetate + NADH + O(2) = 3,4-dihydroxyphenylacetate + NAD(+) + H(2)O. FAD LTB(4) omega-hydroxylase Leukotriene-B(4) omega-hydroxylase Leukotriene-B(4) 20-monooxygenase LTB(4) 20-hydroxylase Leukotriene-B(4) 20-hydroxylase Heme-thiolate (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate + NADPH + O(2) = (6Z,8E,10E,14Z)-(5S,12R)-5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + NADP(+) + H(2)O. Not identical with EC 1.14.13.34. 2-nitrophenol 2-monooxygenase Nitrophenol oxygenase 2-nitrophenol + NADPH + O(2) = catechol + nitrite + NADP(+) + H(2)O. Involved in the metabolism of nitro-aromatic compounds by a strain of Pseudomonas putida. Albendazole sulfoxidase Albendazole monooxygenase Albendazole + NADPH + O(2) = albendazole S-oxide + NADP(+) + H(2)O. FAD 4-hydroxybenzoate 3-hydroxylase 4-hydroxybenzoate 3-monooxygenase (NAD(P)H) The enzyme from Corynebacterium cyclohexanicum is highly specific for 4-hydroxybenzoate, but uses NADH and NADPH at approximately equal rates (cf. EC 1.14.13.2). 4-hydroxybenzoate + NAD(P)H + O(2) = 3,4-dihydroxybenzoate + NAD(P)(+) + H(2)O. FAD It is less specific for NADPH than EC 1.14.13.2. Leukotriene-E(4) 20-monooxygenase Leukotriene-E(4) omega-hydroxylase Also acts on N-acetyl-leukotriene E(4), more slowly. (7E,9E,11Z,14Z)-(5S,6R)-6-(cystein-S-yl)-5-hydroxyicosa-7,9,11,14-tetraenoate + NADPH + O(2) = 20-hydroxyleukotriene E(4) + NADP(+) + H(2)O. Not identical with EC 1.14.13.30. Anthranilate 3-monooxygenase (deaminating) Anthranilate hydroxylase Anthranilate 2,3-hydroxylase (deaminating) Anthranilate + NADPH + O(2) = 2,3-dihydroxybenzoate + NADP(+) + NH(3). The enzyme from Aspergillus niger is an iron protein; that from the yeast Trichosporon cutaneum is a flavoprotein (FAD). 5-O-(4-coumaroyl)-D-quinate/shikimate 3'-hydroxylase 5-O-(4-coumaroyl)-D-quinate 3'-monooxygenase Also acts on trans-5-O-(4-coumaroyl)shikimate. Trans-5-O-(4-coumaroyl)-D-quinate + NADPH + O(2) = trans-5-O-caffeoyl-D-quinate + NADP(+) + H(2)O. Methyltetrahydroprotoberberine 14-monooxygenase Methyltetrahydroprotoberberine 14-hydroxylase (S)-cis-N-methyltetrahydroprotoberberine-14-hydroxylase Heme-thiolate (S)-N-methylcanadine + NADPH + O(2) = allocryptopine + NADP(+) + H(2)O. Anhydrotetracycline oxygenase ATC oxygenase Anhydrotetracycline monooxygenase Anhydrotetracycline + NADPH + O(2) = 12-dehydrotetracycline + NADP(+) + H(2)O. Involved in the biosynthesis of tetracyclines in Streptomyces sp. Endothelium-derived relaxing factor synthase Nitric-oxide synthase NADPH-diaphorase Nitric-oxide synthetase NO synthase Endothelium-derived relaxation factor-forming enzyme The stoichiometry is not clear, but may involve a two-electron and a one-electron oxidation step. L-arginine + n NADPH + m O(2) = citrulline + nitric oxide + n NADP(+). The enzyme in brain, but not that induced in lung or liver by endotoxin, requires calcium. http://purl.uniprot.org/mim/163729 Melilotate 3-monooxygenase 2-hydroxyphenylpropionate hydroxylase Melilotate hydroxylase Melilotic hydroxylase FAD 3-(2-hydroxyphenyl)propanoate + NADH + O(2) = 3-(2,3-dihydroxyphenyl)propanoate + NAD(+) + H(2)O. 2-aminobenzoyl-CoA monooxygenase/reductase Anthraniloyl-CoA monooxygenase FAD 2-aminobenzoyl-CoA + 2 NAD(P)H + O(2) = 2-amino-5-oxocyclohex-1-enecarboxyl-CoA + H(2)O + 2 NAD(P)(+). The non-aromatic product is unstable and releases CO(2) and NH(3), forming 1,4-cyclohexanedione. Tyrosine N-hydroxylase CYP79A1 Tyrosine N-monooxygenase Heme-thiolate (3) N,N-dihydroxy-L-tyrosine = (Z)-(4-hydroxyphenylacetaldehyde oxime) + CO(2) + H(2)O. (1) L-tyrosine + O(2) + NADPH = N-hydroxy-L-tyrosine + NADP(+) + H(2)O. Involved in the biosynthesis of the cyanogenic glucoside dhurrin in sorghum, along with EC 1.14.13.68 and EC 2.4.1.85. Some 2-(4-hydroxyphenyl)-1-nitroethane is formed as a side product. (2) N-hydroxy-L-tyrosine + O(2) + NADPH = N,N-dihydroxy-L-tyrosine + NADP(+) + H(2)O. 4-hydroxyphenylacetonitrile hydroxylase Hydroxyphenylacetonitrile 2-monooxygenase Heme-thiolate 4-hydroxyphenylacetonitrile + NADPH + O(2) = 4-hydroxymandelonitrile + NADP(+) + H(2)O. Questin oxygenase Questin monooxygenase The enzyme cleaves the anthraquinone ring of questin to form a benzophenone. Involved in the biosynthesis of the seco-anthraquinone (+)-geodin. Questin + NADPH + O(2) = sulochrin + NADP(+) + H(2)O. 2-hydroxybiphenyl 3-monooxygenase 2-hydroxybiphenyl + NADH + O(2) = 2,3-dihydroxybiphenyl + NAD(+) + H(2)O. Also converts 2,2'-dihydroxybiphenyl into 2,2',3-trihydroxy-biphenyl. (-)-menthol monooxygenase (-)-menthol + NADPH + O(2) = p-menthane-3,8-diol + NADP(+) + H(2)O. (-)-limonene 3-hydroxylase (-)-limonene 3-monooxygenase (S)-limonene 3-monooxygenase (-)-limonene,NADPH:oxygen oxidoreductase (3-hydroxylating) High specificity, but NADH can act instead of NADPH, although more slowly. (-)-(S)-limonene + NADPH + O(2) = (-)-trans-isopiperitenol + NADP(+) + H(2)O. Heme-thiolate (-)-limonene 6-hydroxylase (-)-limonene,NADPH:oxygen oxidoreductase (6-hydroxylating) (S)-limonene 6-monooxygenase (-)-limonene 6-monooxygenase (-)-(S)-limonene + NADPH + O(2) = (-)-trans-carveol + NADP(+) + H(2)O. Heme-thiolate High specificity, but NADH can act instead of NADPH, although more slowly. (-)-limonene 7-monooxygenase (S)-limonene 7-monooxygenase (-)-limonene monooxygenase (-)-limonene hydroxylase (-)-limonene,NADPH:oxygen oxidoreductase (7-hydroxylating) (-)-(S)-limonene + NADPH + O(2) = (-)-perillyl alcohol + NADP(+) + H(2)O. Heme-thiolate High specificity, but NADH can act instead of NADPH, although more slowly. Imidazoleacetate 4-monooxygenase Imidazoleacetic monooxygenase Imidazoleacetate hydroxylase FAD 4-imidazoleacetate + NADH + O(2) = 5-hydroxy-4-imidazoleacetate + NAD(+) + H(2)O. PCB 4-monooxygenase Pentachlorophenol dehalogenase Pentachlorophenol monooxygenase Pentachlorophenol dechlorinase Pentachlorophenol hydroxylase PCB4MO PCP hydroxylase Pentachlorophenol 4-monooxygenase FAD If C-4 carries a halogen substituent, reaction 1 is catalyzed, e.g. 2,4,6-triiodophenol is oxidized to 2,6-diiodohydroquinone; if C-4 is unsubstituted, reaction 2 is catalyzed. The enzyme displaces a diverse range of substituents from the 4-position of polyhalogenated phenols but requires that a halogen substituent be present at the 2-position. The enzyme converts many polyhalogenated phenols into hydroquinones, and requires that a halogen substituent be present at C-2. (1) Pentachlorophenol + 2 NADPH + O(2) = 2,3,5,6-tetrachlorohydroquinone + 2 NADP(+) + chloride + H(2)O. (2) 2,3,5,6-tetrachlorophenol + NADPH + O(2) = 2,3,5,6-tetrachlorohydroquinone + NADP(+) + H(2)O. 6-oxocineole dehydrogenase 6-oxocineole + NADPH + O(2) = 1,6,6-trimethyl-2,7-dioxabicyclo-[3.2.2]nonan-3-one + NADP(+) + H(2)O. The product undergoes non-enzymic cleavage and subsequent ring closure to form the lactone 4,5-dihydro-5,5-dimethyl-4-(3-oxobutyl)furan-2(3H)-one. Isoflavone 3'-hydroxylase Also acts on biochanin A and other isoflavones with a 4'-methoxy group. Involved in the biosynthesis of the pterocarpin phytoalexins medicarpin and maackiain. Formononetin + NADPH + O(2) = calycosin + NADP(+) + H(2)O. Heme-thiolate Isoflavone 2'-hydroxylase Isoflavone 2'-monooxygenase 4'-methoxyisoflavone 2'-hydroxylase EC 1.14.13.89 is less specific and acts on other isoflavones as well as 4'-methoxyisoflavones. Formononetin + NADPH + O(2) = 2'-hydroxyformononetin + NADP(+) + H(2)O. Involved in the biosynthesis of the pterocarpin phytoalexins medicarpin and maackiain. Heme-thiolate Acts on isoflavones with a 4'-methoxy group, such as formononetin and biochanin A. Steroid-ketone monooxygenase Ketosteroid monooxygenase The possibility that a single enzyme is responsible for the reactions ascribed to EC 1.14.99.4 and EC 1.14.99.12 in other tissues cannot be excluded. (1) Ketosteroid + NADPH + O(2) = steroid ester/lactone + NADP(+) + H(2)O. (3) Androstenedione + NADPH + O(2) = testololactone + NADP(+) + H(2)O. (2) Progesterone + NADPH + O(2) = testosterone acetate + NADP(+) + H(2)O. The oxidative lactonization of a number of derivatives of androstenedione to produce the 13,17-secoandrosteno-17,13-alpha-lactone, such as testololactone, is shown in reaction (3). reaction (2) is also catalyzed by EC 1.14.99.4 and reactions (3) and (4) correspond to that catalyzed by EC 1.14.99.12. The oxidative esterification of a number of derivatives of progesterone to produce the corresponding 17-alpha-hydroxysteroid 17-acetate ester, such as testosterone acetate, is shown in reaction (2). (4) 17-alpha-hydroxyprogesterone + NADPH + O(2) = androstenedione + NADP(+) + H(2)O. FAD The oxidative cleavage of the 17-beta-side-chain of 17-alpha-hydroxyprogesterone to produce androstenedione and acetate is shown in reaction (4). A single FAD-containing enzyme catalyzes three types of monooxygenase (Baeyer-Villiger oxidation) reaction. Protopine 6-monooxygenase Protopine 6-hydroxylase Heme-thiolate Protopine + NADPH + O(2) = 6-hydroxyprotopine + NADP(+) + H(2)O. Involved in benzophenanthridine alkaloid synthesis in higher plants. Dihydrosanguinarine 10-hydroxylase Dihydrosanguinarine 10-monooxygenase Involved in benzophenanthridine alkaloid synthesis in higher plants. Dihydrosanguinarine + NADPH + O(2) = 10-hydroxydihydrosanguinarine + NADP(+) + H(2)O. Heme-thiolate Dihydrochelirubine 12-hydroxylase Dihydrochelirubine 12-monooxygenase Heme-thiolate Dihydrochelirubine + NADPH + O(2) = 12-hydroxydihydrochelirubine + NADP(+) + H(2)O. Benzoyl-CoA 3-hydroxylase Benzoyl-CoA 3-monooxygenase Benzoate is not a substrate. FAD or FMN Benzoyl-CoA + NADPH + O(2) = 3-hydroxybenzoyl-CoA + NADP(+) + H(2)O. L-lysine 6-monooxygenase (NADPH) Lysine N(6)-hydroxylase L-lysine + NADPH + O(2) = N(6)-hydroxy-L-lysine + NADP(+) + H(2)O. The enzyme from strain EN 222 of Escherichia coli is highly specific for L-lysine; L-ornithine and L-homolysine are, for example, not substrates. FAD Orcinol hydroxylase Orcinol 2-monooxygenase FAD Orcinol + NADH + O(2) = 2,3,5-trihydroxytoluene + NAD(+) + H(2)O. 27-hydroxycholesterol 7-alpha-hydroxylase 27-hydroxycholesterol 7-alpha-monooxygenase Heme-thiolate 27-hydroxycholesterol + NADPH + O(2) = 7-alpha,27-dihydroxycholesterol + NADP(+) + H(2)O. The enzyme from mammalian liver differs from EC 1.14.13.17 in having no activity toward cholesterol. 2-oxo-1,2-dihydroquinoline 8-monooxygenase 2-hydroxyquinoline 8-monooxygenase Quinolin-2-ol exists largely as the quinolin-2(1H)-one tautomer. Quinolin-2-ol + NADH + O(2) = quinolin-2,8-diol + NAD(+) + H(2)O. Iron 1-H-4-oxoquinoline 3-monooxygenase Quinolin-4(1H)-one 3-monooxygenase 4-hydroxyquinoline 3-monooxygenase Quinolin-4-ol exists largely as the quinolin-4(1H)-one tautomer. Quinolin-4-ol + NADH + O(2) = quinolin-3,4-diol + NAD(+) + H(2)O. 3-hydroxyphenylacetate 6-monooxygenase 3-hydroxyphenylacetate 6-hydroxylase 3-hydroxyphenylacetate 6-hydroxylase from Flavobacterium sp. is highly specific for 3-hydroxyphenylacetate and uses NADH and NADPH as electron donors with similar efficiency. FAD 3-hydroxyphenylacetate + NAD(P)H + O(2) = 2,5-dihydroxyphenylacetate + NAD(P)(+) + H(2)O. 4-hydroxybenzoate 1-hydroxylase 4-hydroxybenzoate 1-monooxygenase The enzyme from Candida parapsilosis is specific for 4-hydroxybenzoate derivatives and prefers NADH to NADPH as electron donor. 4-hydroxybenzoate + NAD(P)H + O(2) = hydroquinone + NAD(P)(+) + H(2)O + CO(2). FAD 2-hydroxycyclohexanone 2-monooxygenase 2-hydroxycyclohexan-1-one + NADPH + O(2) = 6-hydroxyhexan-6-olide + NADP(+) + H(2)O. The product decomposes spontaneously to 6-oxohexanoic acid (adipic semialdehyde). Nifedipine oxidase Quinine 3-monooxygenase Quinine 3-hydroxylase Quinine + NADPH + O(2) = 3-hydroxyquinine + NADP(+) + H(2)O. Heme-thiolate CYP71E1 4-hydroxyphenylacetaldehyde oxime monooxygenase Cytochrome P450-II-dependent monooxygenase 4-hydroxybenzeneacetaldehyde oxime monooxygenase (Z)-4-hydroxyphenylacetaldehyde oxime + NADPH + O(2) = (S)-4-hydroxymandelonitrile + NADP(+) + 2 H(2)O. Involved in the biosynthesis of the cyanogenic glucoside dhurrin in sorghum, along with EC 1.14.13.41 and EC 2.4.1.85. Heme-thiolate Alkene monooxygenase Alkene epoxygenase Iron Propene + NADH + O(2) = 1,2-epoxypropane + NAD(+) + H(2)O. The enzyme oxygenates C(2) to C(6) aliphatic alkenes. The enzyme from Xanthobacter sp. strain Py2 is a multicomponent enzyme comprising: (1) an NADH reductase, which provides the reductant for O(2) activation. (2) a Rieske-type ferredoxin, which is an electron-transfer protein. (3) an oxygenase, which contains the catalytic center for alkene epoxidation. (4) a small protein of unknown function that is essential for activity. With 1,2-epoxypropane as substrate, the stereospecificity of the epoxypropane formed is 95% (R) and 5% (S). Phenol 2-monooxygenase Phenol hydroxylase Phenol o-hydroxylase Phenol + NADPH + O(2) = catechol + NADP(+) + H(2)O. FAD Also active with resorcinol and o-cresol. Sterol 14-alpha-demethylase Obtusufoliol 14-demethylase Sterol 14-demethylase Lanosterol 14-demethylase Lanosterol 14-alpha-demethylase Cytochrome P450 51 The enzyme (P450) catalyzes successive hydroxylations of the 14-alpha-methyl group and C-15, followed by elimination as formate leaving the 14(15) double bond. Heme-thiolate This enzyme acts on a range of steroids with a 14-alpha-methyl group. Obtusifoliol + 3 O(2) + 3 NADPH = 4-alpha-methyl-5-alpha-ergosta-8,14,24(28)-trien-3-beta-ol + formate + 3 NADP(+) + 4 H(2)O. N-methylcoclaurine 3'-monooxygenase N-methylcoclaurine 3'-hydroxylase Cytochrome P450 80B1 (S)-N-methylcoclaurine 3'-hydroxylase (S)-N-methylcoclaurine + NADPH + O(2) = (S)-3'-hydroxy-N-methylcoclaurine + NADP(+) + H(2)O. A P450 protein involved in benzylisoquinoline alkaloid synthesis in higher plants. Heme-thiolate Methylsterol monooxygenase 4-methylsterol oxidase Methylsterol hydroxylase Also acts on 4-alpha-methyl-5-alpha-cholest-7-en-3-beta-ol. The sterol can be based on cycloartenol as well as lanosterol. (1) 4,4-dimethyl-5-alpha-cholest-7-en-3-beta-ol + NAD(P)H + O(2) = 4-beta-hydroxymethyl-4-alpha-methyl-5-alpha-cholest-7-en-3-beta-ol + NAD(P)(+) + H(2)O. (3) 3-beta-hydroxy-4-beta-methyl-5-alpha-cholest-7-ene-4-alpha-carbaldehyde + NAD(P)H + O(2) = 3-beta-hydroxy-4-beta-methyl-5-alpha-cholest-7-ene-4-alpha-carboxylate + NAD(P)(+) + H(2)O. Requires cytochrome b5. (2) 4-beta-hydroxymethyl-4-alpha-methyl-5-alpha-cholest-7-en-3-beta-ol + NAD(P)H + O(2) = 3-beta-hydroxy-4-beta-methyl-5-alpha-cholest-7-ene-4-alpha-carbaldehyde + NAD(P)(+) + 2 H(2)O. Tabersonine 16-hydroxylase Heme-thiolate Tabersonine + NADPH + O(2) = 16-hydroxytabersonine + NADP(+) + H(2)O. 7-deoxyloganin 7-hydroxylase Heme-thiolate 7-deoxyloganin + NADPH + O(2) = loganin + NADP(+) + H(2)O. Vinorine hydroxylase Heme-thiolate Forms a stage in the biosynthesis of the indole alkaloid ajmaline. Vinorine + NADPH + O(2) = vomilenine + NADP(+) + H(2)O. 5-alpha-taxadienol-10-beta-hydroxylase Taxane 10-beta-hydroxylase Heme-thiolate Taxa-4(20),11-dien-5-alpha-yl acetate + NADPH + O(2) = 10-beta-hydroxytaxa-4(20),11-dien-5-alpha-yl acetate + NADP(+) + H(2)O. Taxane 13-alpha-hydroxylase Taxa-4(20),11-dien-5-alpha-ol + NADPH + O(2) = taxa-4(20),11-dien-5-alpha,13-alpha-diol + NADP(+) + H(2)O. Heme-thiolate Ent-kaurene oxidase (3) Ent-kaur-16-en-19-al + NADPH + O(2) = ent-kaur-16-en-19-oate + NADP(+) + H(2)O. Catalyzes three sucessive oxidations of the 4-methyl group of ent-kaurene giving kaurenoic acid. (2) Ent-kaur-16-en-19-ol + NADPH + O(2) = ent-kaur-16-en-19-al + NADP(+) + 2 H(2)O. (1) Ent-kaur-16-ene + NADPH + O(2) = ent-kaur-16-en-19-ol + NADP(+) + H(2)O. Requires cytochrome P450. Ent-kaurenoic acid oxidase In Cucurbita maxima, ent-6-alpha,7-alpha-dihydroxykaur-16-en-19-oate is also formed. Requires cytochrome P450. (1) Ent-kaur-16-en-19-oate + NADPH + O(2) = ent-7-alpha-hydroxykaur-16-en-19-oate + NADP(+) + H(2)O. (3) Gibberellin A(12) aldehyde + NADPH + O(2) = gibberellin A(12) + NADP(+) + H(2)O. (2) Ent-7-alpha-hydroxykaur-16-en-19-oate + NADPH + O(2) = gibberellin A(12) aldehyde + NADP(+) + 2 H(2)O. The second step includes a ring-B contraction giving the gibbane skeleton. Catalyzes three sucessive oxidations of ent-kaurenoic acid. Flavin mixed function oxidase Flavin-containing monooxygenase FMO FAD-containing monooxygenase Dimethylaniline N-oxidase Dimethylaniline monooxygenase (N-oxide-forming) DMA oxidase Mixed-function amine oxidase Flavin monooxygenase N,N-dimethylaniline monooxygenase Ziegler's enzyme Methylphenyltetrahydropyridine N-monooxygenase Dimethylaniline oxidase For example, N-oxygenation is largely responsible for the detoxification of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). FAD N,N-dimethylaniline + NADPH + O(2) = N,N-dimethylaniline N-oxide + NADP(+) + H(2)O. Is distinct from other monooxygenases in that the enzyme forms a relatively stable hydroperoxy flavin intermediate. http://purl.uniprot.org/mim/602079 A broad spectrum monooxygenase that accepts substrates as diverse as hydrazines, phosphines, boron-containing compounds, sulfides, selenides, iodide, as well as primary, secondary and tertiary amines. Generally converts nucleophilic heteroatom-containing chemicals and drugs into harmless, readily excreted metabolites. (+)-limonene-6-hydroxylase (+)-limonene 6-monooxygenase (R)-limonene 6-monooxygenase Forms part of the carvone biosynthesis pathway in Carum carvi (caraway) seeds. Heme-thiolate (S)-Limonene, the substrate for EC 1.14.13.48 is not a substrate. The reaction is stereospecific with over 95% yield of (+)-trans-carveol from (R)-limonene. http://purl.uniprot.org/mim/609535 (+)-(R)-limonene + NADPH + O(2) = (+)-trans-carveol + NADP(+) + H(2)O. Magnesium-protoporphyrin IX monomethyl ester (oxidative) cyclase Mg-protoporphyrin IX monomethyl ester oxidative cyclase Iron (1) Magnesium-protoporphyrin IX 13-monomethyl ester + NADPH + O(2) = 13(1)-hydroxy-magnesium-protoporphyrin IX 13-monomethyl ester + NADP(+) + H(2)O. The cyclase activity in Chlamydomonas reinhardtii is associated exclusively with the membranes, whereas that from cucumber cotyledons requires both membrane and soluble fractions for activity. (2) 13(1)-hydroxy-magnesium-protoporphyrin IX 13-monomethyl ester + NADPH + O(2) = 13(1)-oxo-magnesium-protoporphyrin IX 13-monomethyl ester + NADP(+) + 2 H(2)O. (3) 13(1)-oxo-magnesium-protoporphyrin IX 13-monomethyl ester + NADPH + O(2) = divinylprotochlorophyllide + NADP(+) + 2 H(2)O. 4-hydroxy-3-methoxybenzoate demethylase Vanillate demethylase Vanillate monooxygenase Vanillate + O(2) + NADH = 3,4-dihydroxybenzoate + NAD(+) + H(2)O + formaldehyde. Forms part of the vanillin degradation pathway in Arthrobacter sp. Precorrin-3X synthase Precorrin-3B synthase In the aerobic cobalamin biosynthesis pathway, four enzymes are involved in the conversion of precorrin-3A to precorrin-6A. Precorrin-3A + NADH + O(2) = precorrin-3B + NAD(+) + H(2)O. This is followed by three methylation reactions, which introduce a methyl group at C-17 (CobJ; EC 2.1.1.131), C-11 (CobM; 2.1.1.133) and C-1 (CobF; EC 2.1.1.152) of the macrocycle, giving rise to precorrin-4, precorrin-5 and precorrin-6A, respectively. Iron-sulfur An oxygen atom from dioxygen is incorporated into the macrocycle at C-20. This enzyme carries out the first of the four steps, yielding precorrin-3B as the product. HAPMO 4-hydroxyacetophenone monooxygenase Highest activity occurs with compounds bearing an electron-donating substituent at the para position of the aromatic ring. (4-hydroxyphenyl)ethan-1-one + NADPH + O(2) = 4-hydroxyphenyl acetate + NADP(+) + H(2)O. In the absence of substrate, the enzyme can act as an NADPH oxidase (EC 1.6.3.1). The enzyme from Pseudomonas fluorescens ACB catalyzes the conversion of a wide range of acetophenone derivatives. FAD Dimethylallyl-3,6a,9-trihydroxypterocarpan cyclase Glyceollin synthase Heme-thiolate 2-(or 4-)dimethylallyl-(6aS,11aS)-3,6a,9-trihydroxypterocarpan + NADPH + O(2) = glyceollin + NADP(+) + 2 H(2)O. Glyceollins II and III are formed from 2-dimethylallyl-(6aS,11aS)-3,6a,9-trihydroxypterocarpan whereas glyceollin I is formed from the 4-isomer. 2-HIS 2-hydroxyisoflavanone synthase Apigenin + 2 NADPH + O(2) = 2-hydroxy-2,3-dihydrogenistein + 2 NADP(+) + H(2)O. Heme-thiolate EC 4.2.1.105 acts on 2-hydroxy-2,3-dihydrogenistein with loss of water and formation of genistein; this may occur spontaneously. Licodione synthase (2S)-flavanone 2-hydroxylase It probably forms 2-hydroxyliquiritigenin which spontaneously forms licodione. Heme-thiolate Liquiritigenin + NADPH + O(2) = licodione + NADP(+) + H(2)O. NADH can act instead of NADPH, but more slowly. Flavonoid 3',5'-hydroxylase F3',5'H F3'5'H Heme-thiolate NADH is not a good substitute for NADPH. (1) A flavanone + NADPH + O(2) = a 3'-hydroxyflavanone + NADP(+) + H(2)O. The enzyme catalyzes the hydroxylation of 5,7,4'-trihydroxyflavanone (naringenin) at either the 3' position to form eriodictyol or at both the 3' and 5' positions to form 5,7,3',4',5'-pentahydroxyflavanone (dihydrotricetin). The enzyme also catalyzes the hydroxylation of 3,5,7,3',4'-pentahydroxyflavanone (taxifolin) at the 5' position, forming ampelopsin. In Petunia hybrida the enzyme acts on naringenin, eriodictyol, dihydroquercetin (taxifolin) and dihydrokaempferol (aromadendrin). The 3',5'-dihydroxyflavanone is formed via the 3'-hydroxyflavanone. (2) A 3'-hydroxyflavanone + NADPH + O(2) = a 3',5'-dihydroxyflavanone + NADP(+) + H(2)O. Isoflavone 2'-hydroxylase Isoflavone 2'-monooxygenase CYP Ge-3 CYP81E1 Acts on daidzein, formononetin and genistein. Heme-thiolate An isoflavone + NADPH + O(2) = a 2'-hydroxyisoflavone + NADP(+) + H(2)O. EC 1.14.13.53 has the same reaction but is more specific as it requires a 4'-methoxyisoflavone. Kynurenine 3-hydroxylase Kynurenine 3-monooxygenase L-kynurenine + NADPH + O(2) = 3-hydroxy-L-kynurenine + NADP(+) + H(2)O. FAD Zeaxanthin epoxidase Zea-epoxidase FAD (2) Antheraxanthin + NAD(P)H + O(2) = violaxanthin + NAD(P)(+) + H(2)O. (1) Zeaxanthin + NAD(P)H + O(2) = antheraxanthin + NAD(P)(+) + H(2)O. It will also epoxidize lutein in some higher-plant species. Along with EC 1.10.99.3, this enzyme forms part of the xanthophyll (or violaxanthin) cycle, which is involved in protecting the plant against damage by excess light. Active under conditions of low light. Deoxysarpagine hydroxylase DOSH Heme-thiolate 10-deoxysarpagine + NADPH + O(2) = sarpagine + NADP(+) + H(2)O. PAMO Phenylacetone monooxygenase In addition to phenylacetone, which is the best substrate found to date, this Baeyer-Villiger monooxygenase can oxidize other aromatic ketones (1-(4-hydroxyphenyl)propan-2-one, 1-(4-hydroxyphenyl)propan-2-one and 3-phenylbutan-2-one), some alipatic ketones (e.g. dodecan-2-one) and sulfides (e.g. 1-methyl-4-(methylsulfanyl)benzene). FAD Phenylacetone + NADPH + O(2) = benzyl acetate + NADP(+) + H(2)O. NADH cannot replace NADPH as coenzyme. (+)-ABA 8'-hydroxylase (+)-abscisic acid 8'-hydroxylase ABA 8'-hydroxylase (+)-abscisate + NADPH + O(2) = 8'-hydroxyabscisate + NADP(+) + H(2)O. CO inhibits the reaction, but its effects can be reversed by the presence of blue light. The 8'-hydroxyabscisate formed can be converted into (-)-phaseic acid, most probably spontaneously. Catalyzes the first step in the oxidative degradation of abscisic acid and is considered to be the pivotal enzyme in controlling the rate of degradation of this plant hormone. Heme-thiolate Other enzymes involved in the abscisic-acid biosynthesis pathway are EC 1.1.1.288, EC 1.2.3.14 and EC 1.13.11.51. Lithocholate 6-beta-hydroxylase Lithocholate 6-beta-monooxygenase 6-beta-hydroxylase Cytochrome P450 3A10/lithocholic acid 6-beta-hydroxylase Expression of the gene for this enzyme is 50-fold higher in male compared to female hamsters. Lithocholate + NADPH + O(2) = 6-beta-hydroxylithocholate + NADP(+) + H(2)O. Heme-thiolate HCO 12-alpha-hydroxylase 7-alpha-hydroxy-4-cholesten-3-one 12-alpha-monooxygenase 7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase Sterol 12-alpha-hydroxylase Requires EC 1.6.2.4 and cytochrome b5 for maximal activity. Heme-thiolate Important in bile acid biosynthesis, being responsible for the balance between the formation of cholic acid and chenodeoxycholic acid. 7-alpha-hydroxycholest-4-en-3-one + NADPH + O(2) = 7-alpha,12-alpha-dihydroxycholest-4-en-3-one + NADP(+) + H(2)O. Sterol 12-alpha-hydroxylase 5-beta-cholestane-3-alpha,7-alpha-diol 12-alpha-monooxygenase Cytochrome P450 8B1 5-beta-cholestane-3-alpha,7-alpha-diol 12-alpha-hydroxylase Can also hydroxylate the substrate at the 25 and 26 position, but to a lesser extent. Key enzyme in the biosynthesis of the bile acid cholic acid (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholanoic acid). Heme-thiolate 5-beta-cholestane-3-alpha,7-alpha-diol + NADPH + O(2) = 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol + NADP(+) + H(2)O. The activity determines the biosynthetic ratio between cholic acid and chenodeoxycholic acid. Taurochenodeoxycholate 6-alpha-hydroxylase Taurochenodeoxycholate 6-alpha-monooxygenase Acts on taurochenodeoxycholate, taurodeoxycholate and less readily on lithocholate and chenodeoxycholate. (1) Taurochenodeoxycholate + NADPH + O(2) = taurohyocholate + NADP(+) + H(2)O. Requires cytochrome b5 for maximal activity. Heme-thiolate In adult pig (Sus scrofa), hyocholic acid replaces cholic acid as a primary bile acid. (2) Lithocholate + NADPH + O(2) = hyodeoxycholate + NADP(+) + H(2)O. Cholesterol 24-hydroxylase Cholesterol 24-monooxygenase Cholesterol 24S-hydroxylase Cytochrome P450 46A1 Heme-thiolate Can also produce 25-hydroxycholesterol. This reaction is the first step in the enzymatic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood-brain barrier whereas cholesterol cannot. Cholesterol + NADPH + O(2) = (24S)-24-hydroxycholesterol + NADP(+) + H(2)O. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol. 24-hydroxycholesterol 7-alpha-monooxygenase 24-hydroxycholesterol 7-alpha-hydroxylase (24R)-cholest-5-ene-3-beta,24-diol + NADPH + O(2) = (24R)-cholest-5-ene-3-beta,7-alpha,24-triol + NADP(+) + H(2)O. Specific for (24R)-cholest-5-ene-3-beta,24-diol as substrate. Heme-thiolate Found in liver microsomes and in ciliary non-pigmented epithelium. With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Flavoprotein-linked monooxygenase Unspecific monooxygenase Cytochrome p450 Aryl hydrocarbon hydroxylase Aryl-4-monooxygenase Xenobiotic monooxygenase Microsomal monooxygenase Microsomal p450 Reactions catalyzed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, N-, S-and O-dealkylations, desulfation, deamination, and reduction of azo, nitro, and N-oxide groups. Acts on a wide range of substrates including many xenobiotics, steroids, fatty acids, vitamins and prostaglandins. Heme-thiolate RH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O. Bacterial luciferase Alkanal monooxygenase (FMN-linked) Aldehyde monooxygenase The reaction involves incorporation of a molecule of oxygen into reduced FMN, and subsequent reaction with the aldehyde to form an activated FMN.H(2)O complex which breaks down with emission of light. RCHO + reduced FMN + O(2) = RCOOH + FMN + H(2)O + light. The enzyme is highly specific for reduced FMN, and for long-chain aliphatic aldehydes with 8 carbons or more. Sulfate starvation-induced protein 6 FMNH(2)-dependent aliphatic sulfonate monooxygenase Alkanesulfonate monooxygenase An alkanesufonate (R-CH(2)-SO(3)H) + FMNH(2) + O(2) = an aldehyde (R-CHO) + FMN + sulfite + H(2)O. Instead, it uses reduced FMN (i.e., FMNH(2)) as a substrate. FMNH(2) is provided by SsuE, the associated FMN reductase (EC 1.5.1.29). Does not use FMN as a bound cofactor. Does not desulfonate taurine (2-aminoethanesulfonate) or aromatic sulfonates. The enzyme from Escherichia coli catalyzes the desulfonation of a wide range of aliphatic sulfonates (unsubstituted C(1)-to C(14)-sulfonates as well as substituted C(2)-sulfonates). With a reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen Camphor 5-monooxygenase Cytochrome p450-cam Camphor 5-exo-methylene hydroxylase (+)-camphor + putidaredoxin + O(2) = (+)-exo-5-hydroxycamphor + oxidized putidaredoxin + H(2)O. Also acts on (-)-camphor and 1,2-campholide, forming 5-exo-hydroxy-1,2-campholide. Heme-thiolate 2,5-diketocamphane lactonizing enzyme Camphor ketolactonase I Camphor 1,2-monooxygenase (+)-bornane-2,5-dione + reduced rubredoxin + O(2) = 5-oxo-1,2-campholide + oxidized rubredoxin + H(2)O. Iron Alkane 1-hydroxylase Lauric acid omega-hydroxylase Fatty acid omega-hydroxylase Alkane 1-monooxygenase Omega-hydroxylase Also hydroxylates fatty acids in the omega-position. Some enzyme of this group are heme-thiolated proteins (P450). Octane + reduced rubredoxin + O(2) = 1-octanol + oxidized rubredoxin + H(2)O. Steroid 11-beta/18-hydroxylase Steroid 11-beta-monooxygenase Steroid 11-beta-hydroxylase Cytochrome p450 XIB1 Heme-thiolate Also hydroxylates steroids at the 18-position, and converts 18-hydroxycorticosterone into aldosterone. A steroid + reduced adrenal ferredoxin + O(2) = an 11-beta-hydroxysteroid + oxidized adrenal ferredoxin + H(2)O. http://purl.uniprot.org/mim/103900 http://purl.uniprot.org/mim/202010 Corticosterone methyl oxidase Corticosterone 18-monooxygenase Corticosterone 18-hydroxylase Heme-thiolate Corticosterone + reduced adrenal ferredoxin + O(2) = 18-hydroxycorticosterone + oxidized adrenal ferredoxin + H(2)O. http://purl.uniprot.org/mim/610600 http://purl.uniprot.org/mim/203400 Cholesterol monooxygenase (side-chain-cleaving) Steroid 20-22 desmolase Cytochrome p450(scc) Cholesterol side-chain-cleaving enzyme Cholesterol side-chain cleavage enzyme Cholesterol desmolase Cholesterol 20-22-desmolase Cholesterol C(20-22) desmolase Steroid 20-22-lyase Cytochrome P-450(scc) The reaction proceeds in three stages, with hydroxylation at C-20 and C-22 preceding scission of the side-chain at C-20. http://purl.uniprot.org/mim/201710 Cholesterol + reduced adrenal ferredoxin + O(2) = pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin + H(2)O. Heme-thiolate Choline monooxygenase The enzyme involved in the second step, EC 1.2.1.8, appears to be the same in plants, animals and bacteria. Iron-sulfur Magnesium In many bacteria, plants and animals, the osmoprotectant betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. In plants, the reaction is catalyzed by this enzyme whereas in animals and many bacteria, it is catalyzed by either membrane-bound choline dehydrogenase (EC 1.1.99.1) or soluble choline oxidase (EC 1.1.3.17). Choline + O(2) + 2 reduced ferredoxin + 2 H(+) = betaine aldehyde hydrate + H(2)O + 2 oxidized ferredoxin. Different enzymes are involved in the first reaction. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 and EC 2.1.1.157. Catalyzes the first step of glycine betaine synthesis. With reduced pteridine as one donor, and incorporation of one atom of oxygen Phenylalanine 4-monooxygenase Phenylalanine hydroxylase Phenylalaninase Phenylalanine 4-hydroxylase PAH http://purl.uniprot.org/mim/261600 Iron The reaction involves an arene oxide which rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained, a process known as the NIH-shift. L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96. Tyrosine hydroxylase L-tyrosine hydroxylase Tyrosine 3-hydroxylase Tyrosine 3-monooxygenase Iron The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin. http://purl.uniprot.org/mim/605407 Activated by phosphorylation, catalyzed by EC 2.7.11.27. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96. L-tyrosine + tetrahydrobiopterin + O(2) = 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin. Anthranilate 3-hydroxylase Anthranilic hydroxylase Anthranilate 3-monooxygenase Anthranilic acid hydroxylase Anthranilate + tetrahydrobiopterin + O(2) = 3-hydroxyanthranilate + dihydrobiopterin + H(2)O. Iron Tryptophan hydroxylase Tryptophan 5-hydroxylase Tryptophan 5-monooxygenase Indoleacetic acid-5-hydroxylase L-tryptophan hydroxylase The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96. L-tryptophan + tetrahydrobiopterin + O(2) = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin. Activated by phosphorylation, catalyzed by a Ca(2+)-activated protein kinase. http://purl.uniprot.org/mim/608516 The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin. Iron Glyceryl etherase Glyceryl-ether cleaving enzyme Glyceryl-ether monooxygenase Requires phospholipids for full activity. 1-alkyl-sn-glycerol + tetrahydrobiopterin + O(2) = 1-hydroxyalkyl-sn-glycerol + dihydrobiopterin + H(2)O. Glutathione The product spontaneously breaks down to form a fatty aldehyde and glycerol. L-mandelate 4-hydroxylase Mandelate 4-monooxygenase Mandelic acid 4-hydroxylase (S)-2-hydroxy-2-phenylacetate + tetrahydrobiopterin + O(2) = (S)-4-hydroxymandelate + dihydrobiopterin + H(2)O. Iron With reduced ascorbate as one donor, and incorporation of one atom of oxygen Dopamine beta-hydroxylase Dopamine beta-monooxygenase 3,4-dihydroxyphenethylamine + ascorbate + O(2) = noradrenaline + dehydroascorbate + H(2)O. Stimulated by fumarate. http://purl.uniprot.org/mim/223360 Copper PAM Peptidylglycine 2-hydroxylase Peptidylglycine alpha-amidating monooxygenase Peptidylglycine monooxygenase Peptidyl alpha-amidating enzyme Copper Peptidylglycine + ascorbate + O(2) = peptidyl(2-hydroxyglycine) + dehydroascorbate + H(2)O. The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide, a reaction catalyzed by EC 4.3.2.5. Involved in the final step of biosynthesis of alpha-melanotropin and related biologically active peptides. Peptidylglycines with a neutral amino acid residue in the penultimate position are the best substrates for the enzyme. 1-aminocyclopropane-1-carboxylate oxidase ACC oxidase Aminocyclopropanecarboxylate oxidase Ethylene-forming enzyme In the enzyme from plants, the ethylene has signaling functions such as stimulation of fruit-ripening. Requires CO(2) for activity. Iron 1-aminocyclopropane-1-carboxylate + ascorbate + O(2) = ethylene + cyanide + dehydroascorbate + CO(2) + 2 H(2)O. With another compound as one donor, and incorporation of one atom of oxygen Phenolase Monophenol oxidase Cresolase Monophenol monooxygenase Tyrosinase http://purl.uniprot.org/mim/203100 A group of copper proteins that also catalyze the reaction of EC 1.10.3.1, if only 1,2-benzenediols are available as substrate. http://purl.uniprot.org/mim/606952 L-tyrosine + L-dopa + O(2) = L-dopa + dopaquinone + H(2)O. Copper http://purl.uniprot.org/mim/103470 CMP-N-acetylneuraminate hydroxylase CMP-Neu5Ac hydroxylase CMP-N-acetylneuraminate monooxygenase Cytidine monophosphoacetylneuraminate monooxygenase CMP-N-acetylneuraminic acid hydroxylase The enzyme can be activated by Fe(2+) or Fe(3+). Iron Iron-sulfur The ferricytochrome b5 produced is reduced by NADH and EC 1.6.2.2. CMP-N-acetylneuraminate + 2 ferrocytochrome b5 + O(2) + 2 H(+) = CMP-N-glycoloylneuraminate + 2 ferricytochrome b5 + H(2)O. With oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water Stearoyl-CoA 9-desaturase Fatty acid desaturase Stearoyl-CoA desaturase Delta(9)-desaturase Acyl-CoA desaturase The ferricytochrome b5 produced is reduced by NADH and EC 1.6.2.2. Stearoyl-CoA + 2 ferrocytochrome b5 + O(2) + 2 H(+) = oleoyl-CoA + 2 ferricytochrome b5 + 2 H(2)O. Iron The liver enzyme is an enzyme system involving cytochrome b5 and EC 1.6.2.2. Acyl-[acyl-carrier-protein] desaturase Stearyl-ACP desaturase Stearyl acyl carrier protein desaturase Requires ferredoxin. Stearoyl-[acyl-carrier-protein] + reduced acceptor + O(2) = oleoyl-[acyl-carrier-protein] + acceptor + 2 H(2)O. The enzyme from safflower is specific for stearoyl-CoA; that from Euglena acts on derivatives of a number of long-chain fatty acids. Linoleoyl-coenzyme A desaturase Delta(6)-desaturase Fatty acid Delta(6)-desaturase Linoleate desaturase Linoleic acid desaturase Fatty acid 6-desaturase Delta(6)-fatty acyl-CoA desaturase Long-chain fatty acid Delta(6)-desaturase Linoleoyl CoA desaturase Linoleic desaturase Linoleoyl-CoA desaturase Delta(6)-acyl CoA desaturase Linoleoyl-CoA + AH(2) + O(2) = gamma-linolenoyl-CoA + A + 2 H(2)O. Iron The rat liver enzyme is an enzyme system involving cytochrome b5 and EC 1.6.2.2. With 2-oxoglutarate as one donor, and the other dehydrogenated Penicillin N expandase DAOCS DAOC synthase Deacetoxycephalosporin-C synthase Penicillin N + 2-oxoglutarate + O(2) = deacetoxycephalosporin C + succinate + CO(2) + H(2)O. Forms part of the penicillin biosynthesis pathway. With NADH or NADPH as one donor, and the other dehydrogenated (S)-cheilanthifoline oxidase (methylenedioxy-bridge-forming) (S)-stylopine synthase Catalyzes an oxidative reaction that does not incorporate oxygen into the product. Forms the second methylenedioxy bridge of the protoberberine alkaloid stylopine from oxidative ring closure of adjacent phenolic and methoxy groups of cheilanthifoline. (S)-cheilanthifoline + NADPH + O(2) = (S)-stylopine + NADP(+) + 2 H(2)O. Heme-thiolate (S)-scoulerine oxidase (methylenedioxy-bridge-forming) (S)-cheilanthifoline synthase Catalyzes an oxidative reaction that does not incorporate oxygen into the product. Heme-thiolate Forms the methylenedioxy bridge of the protoberberine alkaloid cheilanthifoline from oxidative ring closure of adjacent phenolic and methoxy groups of scoulerine. (S)-scoulerine + NADPH + O(2) = (S)-cheilanthifoline + NADP(+) + 2 H(2)O. Berbamunine synthase (S)-N-methylcoclaurine oxidase (C-O phenol-coupling) Reaction of 2 molecules of (R)-N-methylcoclaurine gives the dimer guattagaumerine. Heme-thiolate (S)-N-methylcoclaurine + (R)-N-methylcoclaurine + NADPH + O(2) = berbamunine + NADP(+) + 2 H(2)O. Forms the bisbenzylisoquinoline alkaloid berbamunine by phenol oxidation of N-methylcoclaurine without the incorporation of oxygen into the product. Salutaridine synthase (R)-reticuline oxidase (C-C phenol-coupling) Forms the morphinan alkaloid salutaridine by intramolecular phenol oxidation of reticuline without the incorporation of oxygen into the product. Heme-thiolate (R)-reticuline + NADPH + O(2) = salutaridine + NADP(+) + 2 H(2)O. (S)-tetrahydrocolumbamine oxidase (methylenedioxy-bridge-forming) (S)-canadine synthase (S)-tetrahydroberberine synthase Catalyzes an oxidative reaction that does not incorporate oxygen into the product. Heme-thiolate Oxidation of the methoxyphenol group of the alkaloid tetrahydrocolumbamine results in the formation of the methylenedioxy bridge of canadine. (S)-tetrahydrocolumbamine + NADPH + O(2) = (S)-canadine + NADP(+) + 2 H(2)O. Lathosterol 5-desaturase Delta(7)-sterol 5-desaturase 5-DES Delta(7)-sterol Delta(5)-dehydrogenase Lathosterol oxidase Delta(7)-sterol-C5(6)-desaturase This enzyme catalyzes the introduction of a C5 double bond into the B ring of Delta(7)-sterols to yield the corresponding Delta(5,7)-sterols in mammals, yeast and plants. http://purl.uniprot.org/mim/607330 5-alpha-cholest-7-en-3-beta-ol + NAD(P)H + O(2) = cholesta-5,7-dien-3-beta-ol + NAD(P)(+) + 2 H(2)O. Forms part of the plant sterol biosynthesis pathway. Miscellaneous (requires further characterization) PG synthetase Prostaglandin G/H synthase Prostaglandin-endoperoxide synthase Prostaglandin synthase Prostaglandin synthetase Acts both as a dioxygenase and as a peroxidase. Arachidonate + AH(2) + 2 O(2) = prostaglandin H(2) + A + H(2)O. Steroid 21-hydroxylase Cytochrome p450 XXIA1 Steroid 21-monooxygenase A steroid + AH(2) + O(2) = a 21-hydroxysteroid + A + H(2)O. http://purl.uniprot.org/mim/201910 Heme-thiolate Estradiol 6-beta-monooxygenase Estradiol 6-beta-hydroxylase Estradiol-17-beta + AH(2) + O(2) = 6-beta-hydroxyestradiol-17-beta + A + H(2)O. Androstenedione monooxygenase Androstene-3,17-dione hydroxylase 4-androstene-3,17-dione monooxygenase Androst-4-ene-3,17-dione monooxygenase Androst-4-ene-3,17-dione 17-oxidoreductase Androst-4-ene-3,17-dione + AH(2) + O(2) = 3-oxo-13,17-secoandrost-4-ene-17,13-alpha-lactone + A + H(2)O. A single enzyme from Cylindrocarpon radicicola (EC 1.14.13.54) catalyzes both this reaction and that catalyzed by EC 1.14.99.4. Has a wide specificity. Progesterone 11-alpha-monooxygenase Progesterone 11-alpha-hydroxylase Progesterone + AH(2) + O(2) = 11-alpha-hydroxyprogesterone + A + H(2)O. 4-methoxybenzoate O-demethylase 4-methoxybenzoate monooxygenase (O-demethylating) Also acts on 4-ethoxybenzoate, N-methyl-4-aminobenzoate and toluate. The fungal enzyme acts best on veratrate. Iron-sulfur Flavoprotein The bacterial enzyme consists of a ferredoxin-type protein and an iron-sulfur flavoprotein (FMN). 4-methoxybenzoate + AH(2) + O(2) = 4-hydroxybenzoate + formaldehyde + A + H(2)O. Plasmanylethanolamine desaturase Alkylacylglycerophosphoethanolamine desaturase Either NADPH or NADH can act as AH(2). Requires ATP. May involve cytochrome b5. O-1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine + AH(2) + O(2) = O-1-alk-1-enyl-2-acyl-sn-glycero-3-phosphoethanolamine + A + 2 H(2)O. Magnesium Kynurenine 7,8-hydroxylase Kynurenate + AH(2) + O(2) = 7,8-dihydro-7,8-dihydroxykynurenate + A. Phylloquinone epoxidase Phylloquinone monooxygenase (2,3-epoxidizing) Phylloquinone + AH(2) + O(2) = 2,3-epoxyphylloquinone + A + H(2)O. Latia-luciferin monooxygenase (demethylating) Flavoprotein The reaction possibly involves two enzymes, an oxygenase followed by a monooxygenase for the actual light-emitting step. Latia luciferin is (E)-2-methyl-4-(2,6,6-trimethyl-1-cyclohex-1-yl)-1-buten-1-ol formate. Latia luciferin + AH(2) + 2 O(2) = oxidized Latia luciferin + CO(2) + formate + A + H(2)O + light. Ecdysone 20-monooxygenase Ecdysone + AH(2) + O(2) = 20-hydroxyecdysone + A + H(2)O. Heme-thiolate An enzyme from insect fat body or malpighian tubules. NADPH can act as ultimate hydrogen donor. 3-hydroxybenzoate 2-hydroxylase 3-hydroxybenzoate 2-monooxygenase 3-hydroxybenzoate + AH(2) + O(2) = 2,3-dihydroxybenzoate + A + H(2)O. Steroid 9-alpha-hydroxylase Steroid 9-alpha-monooxygenase Pregna-4,9(11)-diene-3,20-dione + AH(2) + O(2) = 9,11-alpha-epoxypregn-4-ene-3,20-dione + A + H(2)O. Iron-sulfur FMN An enzyme system involving a flavoprotein (FMN) and two iron-sulfur proteins. 2-hydroxypyridine oxygenase 2-hydroxypyridine 5-monooxygenase Also oxidizes 2,5-dihydroxypyridine, but does not act on 3-hydroxypyridine, 4-hydroxypyridine or 2,6-dihydroxypyridine. 2-hydroxypyridine + AH(2) + O(2) = 2,5-dihydroxypyridine + A + H(2)O. Juglone 3-monooxygenase Also acts on 1,4-naphthoquinone, naphthazarin and 2-chloro-1,4-naphthoquinone, but not on other related compounds. 5-hydroxy-1,4-naphthoquinone + AH(2) + O(2) = 3,5-dihydroxy-1,4-naphthoquinone + A + H(2)O. Linalool 8-monooxygenase Heme-thiolate 3,7-dimethylocta-1,6-dien-3-ol + AH(2) + O(2) = (E)-3,7-dimethylocta-1,6-dien-3,8-diol + A + H(2)O. Deoxyhypusine dioxygenase DOHH Deoxyhypusine monooxygenase Deoxyhypusine hydroxylase Protein N(6)-(4-aminobutyl)-L-lysine + AH(2) + O(2) = protein N(6)-((R)-4-amino-2-hydroxybutyl)-L-lysine + A + H(2)O. Catalyzes the final step in the formation of the amino acid hypusine in eukaryotic initiation factor 5A (eIF-5A) (formerly eIF-4D). Heme oxygenase (decyclizing) Heme oxygenase Heme oxidase The central iron is kept in the reduced state by NAD(P)H. Heme + 3 AH(2) + 3 O(2) = biliverdin + Fe(2+) + CO + 3 A + 3 H(2)O. http://purl.uniprot.org/mim/141250 The third oxygen molecule provides the oxygen atom that converts the alpha-carbon to CO. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules. Requires NAD(P)H and EC 1.6.2.4. Carotene 7,8-desaturase Zeta-carotene desaturase Neurosporene + AH(2) + O(2) = lycopene + A + 2 H(2)O. Also acts on zeta-carotene twice to give lycopene and converts beta-zeacarotene to gamma-carotene, and pro-zeta-carotene to prolycopene (via double reaction). Myristoyl-CoA 11-(E) desaturase EC 1.14.99.32 forms the Z-isomer by stereospecific cleavage of pro-R H at C-11 and C-12. Myristoyl-CoA + NAD(P)H + O(2) = (E)-11-tetradecenoyl-CoA + NAD(P)(+) + 2 H(2)O. Involved in sex pheromone synthesis in Spodoptera littoralis. (E)-11-tetradecenoyl-CoA is formed by stereospecific removal of the pro-R H at C-11 and the pro-S H at C-12. Myristoyl-CoA 11-(Z) desaturase Involved in sex pheromone synthesis in Spodoptera littoralis. Myristoyl-CoA + NAD(P)H + O(2) = (Z)-11-tetradecenoyl-CoA + NAD(P)(+) + 2 H(2)O. (Z)-11-tetradecenoyl-CoA is formed by stereospecific removal of H from the pro-R positions at C-11 and C-12. EC 1.14.99.31 forms the E-isomer by removing the pro-R H group at C-11 and the pro-S H group at C-12. Delta-12 fatty acid acetylenase Linoleate Delta-12-fatty acid acetylenase (desaturase) Crepenynate synthase Delta(12)-fatty acid dehydrogenase Linoleate + AH(2) + O(2) = crepenynate + A + H(2)O. Iron Monoprenyl isoflavone epoxidase Monoprenyl isoflavone monooxygenase The enzyme has a high specificity for monoprenyl isoflavone. It is slowly and nonenzymically converted into the corresponding dihydrofurano derivative. The product of the prenyl epoxidation reaction contains an oxygen atom derived from O(2), but not from H(2)O. 7-O-methylluteone + NADPH + O(2) = dihydrofurano derivatives + NADP(+) + H(2)O. FAD Thiophene-2-carboxyl-CoA hydroxylase Thiophene-2-carbonyl-CoA monooxygenase Thiophene-2-carboxyl-CoA dehydrogenase Thiophene-2-carboxyl-CoA monooxygenase Thiophene-2-carbonyl-CoA + AH(2) + O(2) = 5-hydroxythiophene-2-carbonyl-CoA + A + H(2)O. Highly specific for thiophene-2-carbonyl-CoA. Molybdenum Tetrazolium salts can act as electron acceptors. Carotene 15,15'-dioxygenase Carotene dioxygenase Beta-carotene 15,15'-monooxygenase Beta-carotene 15,15'-dioxygenase The reaction proceeds in three stages, epoxidation of the 15,15'-double bond, hydration of the double bond leading to ring opening, and oxidative cleavage of the diol formed (cf. EC 1.14.15.6). Beta-carotene + O(2) = 2 retinal. Bile salts Iron Thus only one atom of the dioxygen is incorporated into retinal. Taxadiene 5-alpha-hydroxylase The reaction includes rearrangement of the 4(5)-double bond to a 4(20)-double bond, possibly through allylic oxidation. Requires P450. Taxa-4,11-diene + AH(2) + O(2) = taxa-4(20),11-dien-5-alpha-ol + A + H(2)O. Cholesterol 25-hydroxylase Cholesterol 25-monooxygenase Cholesterol + AH(2) + O(2) = 25-hydroxycholesterol + A + H(2)O. In cell cultures, this enzyme down-regulates cholesterol synthesis and the processing of sterol regulatory element binding proteins (SREBPs). Instead, it uses diiron cofactors to catalyze the hydroxylation of hydrophobic substrates. Iron The diiron cofactor can be either Fe-O-Fe or Fe-OH-Fe and is bound to the enzyme through interactions with clustered histidine or glutamate residues. Unlike most other sterol hydroxylases, this enzyme is not a cytochrome P-450. Progesterone hydroxylase Progesterone monooxygenase Has a wide specificity. A single enzyme from Cylindrocarpon radicicola (EC 1.14.13.54) catalyzes both this reaction and that catalyzed by EC 1.14.99.12. Progesterone + AH(2) + O(2) = testosterone acetate + A + H(2)O. Squalene epoxidase Squalene monooxygenase This enzyme, together with EC 5.4.99.7, was formerly known as squalene oxidocyclase. Squalene + AH(2) + O(2) = (S)-squalene-2,3-epoxide + A + H(2)O. FAD Steroid 17-alpha-monooxygenase Steroid 17-alpha-hydroxylase Cytochrome p450 XVIIA1 Steroid 17-alpha-hydroxylase/17,20 lyase Heme-thiolate A steroid + AH(2) + O(2) = a 17-alpha-hydroxysteroid + A + H(2)O. http://purl.uniprot.org/mim/202110 Acting on superoxide as acceptor Acting on superoxide as acceptor Superoxide dismutase http://purl.uniprot.org/mim/105400 Copper and zinc or iron or manganese 2 superoxide + 2 H(+) = O(2) + H(2)O(2). Superoxide reductase Desulfoferrodoxin Neelaredoxin Reduced rubredoxin + superoxide + 2 H(+) = rubredoxin + H(2)O(2). Iron Oxidizing metal ions With NAD(+) or NADP(+) as acceptor Mercury(II) reductase Mercuric reductase Hg + NADP(+) + H(+) = Hg(2+) + NADPH. Transferrin reductase Diferric-transferrin reductase Transferrin-[Fe(2+)](2) + NAD(+) = transferrin-[Fe(3+)](2) + NADH. Aquocobalamin reductase Vitamin B(12a) reductase Aquacobalamin reductase B(12a) reductase NADH:cob(III)alamin oxidoreductase NADH-linked aquacobalamin reductase Flavoprotein 2 cob(II)alamin + NAD(+) = 2 aquacob(III)alamin + NADH. Cob(II)alamin reductase B(12r) reductase NADH:cob(II)alamin oxidoreductase Vitamin B(12r) reductase Flavoprotein 2 cob(I)alamin + NAD(+) = 2 cob(II)alamin + NADH. Aquacobalamin reductase (NADPH) NADPH:aquacob(III)alamin oxidoreductase Aquacobalamin (reduced nicotinamide adenine dinucleotide phosphate) reductase NADPH-linked aquacobalamin reductase Acts on aquacob(III)alamin and hydroxycobalamin, but not on cyanocobalamin. 2 cob(II)alamin + NADP(+) = 2 aquacob(III)alamin + NADPH. Flavoprotein Cyanocobalamin reductase (NADPH; CN-eliminating) Cyanocobalamin reductase Cyanocobalamin reductase (cyanide-eliminating) Cyanocobalamin reductase (NADPH, cyanide-eliminating) NADPH:cyanocob(III)alamin oxidoreductase (cyanide-eliminating) Cob(I)alamin + cyanide + NADP(+) = cyanocob(III)alamin + NADPH. Flavoprotein Ferric chelate reductase NADH:Fe(3+) oxidoreductase Iron chelate reductase Ferric-chelate reductase NADH:Fe(3+)-EDTA reductase 2 Fe(2+) + NAD(+) = 2 Fe(3+) + NADH. Involved in the transport of iron across plant plasma membranes. FAD Methionine synthase cob(II)alamin reductase (methylating) [Methionine synthase] reductase [Methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing) Methionine synthase reductase FAD The substrate of the enzyme is the inactivated [Co(II)] form of EC 2.1.1.13. FMN Electrons are transferred from NADPH to FAD to FMN. 2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP(+) = 2 [methionine synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine. http://purl.uniprot.org/mim/236270 With oxygen as acceptor Ferroxidase Ceruloplasmin 4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O. http://purl.uniprot.org/mim/604290 Copper http://purl.uniprot.org/mim/134770 With flavin as acceptor Cob(II)yrinic acid a,c-diamide reductase 2 cob(II)yrinic acid a,c-diamide + FMN + 2 H(+) = 2 cob(I)yrinic acid a,c-diamide + FMNH(2). Also uses FAD and NADH but not NADPH. This enzyme also catalyzes the reduction of cob(II)yric acid, cob(II)inamide, cob(II)inamide phosphate, GDP-cob(II)inamide and cob(II)alamin although cob(II)yrinic acid a,c-diamide is thought to be the physiological substrate. Acting on CH or CH(2) groups With NAD(+) or NADP(+) as acceptor CDP-4-keto-deoxy-glucose reductase Cytidine diphospho-4-keto-6-deoxy-D-glucose reductase NAD(P)H:CDP-4-keto-6-deoxy-D-glucose oxidoreductase CDP-4-dehydro-6-deoxyglucose reductase Cytidine diphosphate 4-keto-6-deoxy-D-glucose-3-dehydrogenase CDP-4-keto-6-deoxyglucose reductase CDP-4-keto-6-deoxy-D-glucose-3-dehydrogenase system The enzyme consists of two proteins. The second catalyzes the reduction of this adduct by NAD(P)H and release of the CDP-4-dehydro-3,6-dideoxy-D-glucose and pyridoxamine phosphate. CDP-4-dehydro-3,6-dideoxy-D-glucose + NAD(P)(+) + H(2)O = CDP-4-dehydro-6-deoxy-D-glucose + NAD(P)H. One forms an enzyme-bound adduct of the CDP-4-dehydro-6-deoxyglucose with pyridoxamine phosphate, in which the 3-hydroxy group has been removed. 4-hydroxy-3-methylbut-2-enyl diphosphate reductase Forms part of an alternative, nonmevalonate pathway for terpenoid biosynthesis. The enzyme acts in the reverse direction producing a 5:1 mixture of isopentenyl diphosphate and dimethyallyl diphosphate. Isopentenyl diphosphate + NAD(P)(+) + H(2)O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H. Leucocyanidin reductase Leucoanthocyanidin reductase While 2,3-trans-3,4-cis-leucocyanidin is the preferred flavan-3,4-diol substrate, 2,3-trans-3,4-cis-leucodelphinidin and 2,3-trans-3, 4-cis-leucopelargonidin can also act as substrates, but more slowly. Catalyzes the synthesis of catechin-4-beta-ol and the related flavan-3-ols afzelechin and gallocatechin, which are initiating monomers in the synthesis of plant polymeric proanthocyanidins or condensed tannins. (2R,3S)-catechin + NADP(+) + H(2)O = 2,3-trans-3,4-cis-leucocyanidin + NADPH. NADH can replace NADPH but is oxidized more slowly. Xanthine oxidoreductase Xanthine dehydrogenase Xanthine/NAD(+) oxidoreductase Xanthine-NAD oxidoreductase NAD-xanthine dehydrogenase Xanthine + NAD(+) + H(2)O = urate + NADH. FAD The animal enzyme can be interconverted to EC 1.17.3.2 (the oxidase form). Iron-sulfur Acts on a variety of purines and aldehydes, including hypoxanthine. This enzyme can also be converted into EC 1.17.3.2 by EC 1.8.4.7 in the presence of glutathione disulfide. In other animal tissues, the enzyme exists almost entirely as EC 1.17.3.2, but can be converted into the dehydrogenase form by 1,4-dithioerythritol. That from liver exists in vivo mainly in the dehydrogenase form, but can be converted into EC 1.17.3.2 by storage at -20 degrees Celsius, by treatment with proteolytic agents or organic solvents, or by thiol reagents such as Cu(2+), N-ethylmaleamide or 4-hydroxymercuribenzoate. http://purl.uniprot.org/mim/278300 The effect of thiol reagents can be reversed by thiols such as 1,4-dithioerythritol. Molybdenum Nicotinate hydroxylase Nicotinate dehydrogenase Nicotinic acid hydroxylase Flavoprotein Nicotinate + H(2)O + NADP(+) = 6-hydroxynicotinate + NADPH. Other enzymes involved in this pathway are EC 1.3.7.1, EC 3.5.2.18, EC 1.1.1.291, EC 5.4.99.4, EC 5.3.3.6, EC 4.2.1.85 and EC 4.1.3.32. The enzyme from Clostridium barkeri also possesses a catalytically essential, labile selenium that can be removed by reaction with cyanide. Forms part of the nicotinate-fermentation catabolism pathway in Eubacterium barkeri. The enzyme is capable of acting on a variety of nicotinate analogs to varying degrees, including pyrazine-2-carboxylate, pyrazine 2,3-dicarboxylate, trigonelline and 6-methylnicotinate. Iron With oxygen as acceptor Pteridine oxidase Different from EC 1.17.3.2. 2-amino-4-hydroxypteridine + O(2) = 2-amino-4,7-dihydroxypteridine + (?). Does not act on hypoxanthine. Xanthine oxidoreductase Hypoxanthine:oxygen oxidoreductase Schardinger enzyme Xanthine:O(2) oxidoreductase Hypoxanthine-xanthine oxidase Xanthine:xanthine oxidase Xanthine oxidase Hypoxanthine oxidase That from liver exists in vivo mainly as the dehydrogenase form, but can be converted into the oxidase form by storage at -20 degrees Celsius, by treatment with proteolytic enzymes or with organic solvents, or by thiol reagents such as Cu(2+), N-ethylmaleamide or 4-mercuribenzoate. Xanthine + H(2)O + O(2) = urate + H(2)O(2). The Micrococcus enzyme can use ferredoxin as acceptor. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes (i.e. possesses the activity of EC 1.2.3.1). http://purl.uniprot.org/mim/278300 Molybdopterin FAD Iron-sulfur The enzyme from animal tissues can be converted into EC 1.17.1.4. The effect of thiol reagents can be reversed by thiols such as 1,4-dithioerythritol. EC 1.17.1.4 can also be converted into this enzyme by EC 1.8.4.7 in the presence of glutathione disulfide. Under some conditions the product is mainly superoxide rather than peroxide: R-H + H(2)O + 2 O(2) = ROH + 2 O(2)(.-) + 2 H(+). 6-hydroxynicotinate hydroxylase 6-hydroxynicotinic acid dehydrogenase 6-hydroxynicotinate dehydrogenase 6-hydroxynicotinic acid hydroxylase 6-hydroxynicotinate + H(2)O + O(2) = 2,6-dihydroxynicotinate + H(2)O(2). Iron-sulfur Molybdopterin FAD The enzyme also has a catalytically essential, labile selenium that can be removed by reaction with cyanide. In Bacillus niacini, this enzyme is required for growth on nicotinic acid. With a disulfide as acceptor Ribonucleotide reductase Ribonucleoside-diphosphate reductase ATP Iron 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin. Ribonucleoside-triphosphate reductase Ribonucleotide reductase ATP Cobalt 2'-deoxyribonucleoside triphosphate + thioredoxin disulfide + H(2)O = ribonucleoside triphosphate + thioredoxin. 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + H(2)O + protein-disulfide = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + protein-dithiol. Forms, in the reverse direction, part of an alternative, nonmevalonate pathway for terpenoid biosynthesis. With a quinone or similar compound as acceptor Phenylacetyl-CoA dehydrogenase Phenylacetyl-CoA:acceptor oxidoreductase Phenylacetate, acetyl-CoA, benzoyl-CoA, propanoyl-CoA, crotonyl-CoA, succinyl-CoA and 3-hydroxybenzoyl-CoA cannot act as substrates. The enzyme is specific for phenylacetyl-CoA as substrate. Iron-sulfur Molybdopterin The oxygen atom introduced into the product, phenylglyoxylyl-CoA, is derived from water and not molecular oxygen. Duroquinone, menaquinone and 2,6-dichlorophenolindophenol (DCPIP) can act as acceptor, but the likely physiological acceptor is ubiquinone. A second enzyme, EC 3.1.2.25 converts the phenylglyoxylyl-CoA formed into phenylglyoxylate. Phenylacetyl-CoA + H(2)O + 2 quinone = phenylglyoxylyl-CoA + 2 quinol. With other acceptors 4-cresol dehydrogenase (hydroxylating) p-cresol-(acceptor) oxidoreductase (hydroxylating) p-cresol methylhydroxylase FAD 4-cresol + acceptor + H(2)O = 4-hydroxybenzaldehyde + reduced acceptor. A quinone methide is probably formed as intermediate. The first hydroxylation forms 4-hydroxybenzyl alcohol; a second hydroxylation converts this into 4-hydroxybenzaldehyde. Phenazine methosulfate can act as acceptor. Ethylbenzene hydroxylase Ethylbenzene dehydrogenase Toluene is not oxidized. Ethylbenzene + H(2)O + acceptor = (S)-1-phenylethanol + reduced acceptor. Heme p-benzoquinone or ferrocenium can act as electron acceptor. Iron-sulfur Involved in the anaerobic catabolism of ethylbenzene by denitrifying bacteria. Molybdopterin Ethylbenzene is the preferred substrate; the enzyme from some strains oxidizes propylbenzene, 1-ethyl-4-fluorobenzene, 3-methylpent-2-ene and ethylidenecyclohexane. 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA oxidase THCA-CoA oxidase 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA 24-hydroxylase Trihydroxycoprostanoyl-CoA oxidase THC-CoA oxidase 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-oate 24-hydroxylase However, in amphibians such as the Oriental fire-bellied toad (Bombina orientalis), it is probable that the product is formed via direct hydroxylation of the saturated side chain of (25R)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-oate and not via hydration of a 24(25) double bond. Requires ATP. The reaction in mammals possibly involves dehydrogenation to give a 24(25)-double bond followed by hydration. (25R)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-oyl-CoA + H(2)O + acceptor = (24R,25R)-3-alpha,7-alpha,12-alpha,24-tetrahydroxy-5-beta-cholestan-26-oyl-CoA + reduced acceptor. In microsomes, the free acid is preferred to the coenzyme A ester, whereas in mitochondria, the coenzyme A ester is preferred to the free-acid form of the substrate. Uracil/thymine dehydrogenase Uracil-thymine oxidase Uracil dehydrogenase Uracil oxidase (1) Uracil + H(2)O + acceptor = barbiturate + reduced acceptor. Mammals, plants and other microorganisms utilize the reductive pathway, comprising EC 1.3.1.1 or EC 1.3.1.2, EC 3.5.2.2 and EC 3.5.1.6, with the ultimate degradation products being an L-amino acid, NH(3) and CO(2). (2) Thymine + H(2)O + acceptor = 5-methylbarbiturate + reduced acceptor. Forms part of the oxidative pyrimidine-degrading pathway in some microorganisms, along with EC 3.5.2.1 and EC 3.5.1.95. Bile-acid 7-alpha-dehydroxylase 7-alpha-dehydroxylase Cholate 7-alpha-dehydroxylase Bile acid 7-dehydroxylase This unusual regulation by the NAD(+)/NADH ratio is most likely the result of the intermediates being linked at C-24 by an anhydride bond to the 5'-diphosphate of 3'-phospho-ADP. Highly specific for bile-acid substrates and requires a free C-24 carboxy group and an unhindered 7-alpha-hydroxy group on the B-ring of the steroid nucleus for activity, as found in cholate and chenodeoxycholate. The reaction is stimulated by the presence of NAD(+) but is inhibited by excess NADH. (1) Deoxycholate + FAD + H(2)O = cholate + FADH(2). Under physiological conditions, the reactions occur in the reverse direction to that shown above. Allo-deoxycholate is also formed as a side-product of the 7-alpha-dehydroxylation of cholate. (2) Lithocholate + FAD + H(2)O = chenodeoxycholate + FADH(2). Acting on iron-sulfur proteins as donors With NAD(+) or NADP(+) as acceptor Rubredoxin reductase Dihydronicotinamide adenine dinucleotide--rubredoxin reductase Rubredoxin--NAD reductase Rubredoxin--NAD(+) reductase Rubredoxin--nicotinamide adenine dinucleotide reductase NADH--rubredoxin oxidoreductase NADH--rubredoxin reductase Reduced nicotinamide adenine dinucleotide--rubredoxin reductase FAD 2 reduced rubredoxin + NAD(+) = 2 oxidized rubredoxin + NADH. Iron The reaction does not occur when NADPH is substituted for NADH. The enzyme from Clostridium acetobutylicum reduces rubredoxin, ferricyanide and dichlorophenolindophenol, but not ferredoxin or flavodoxin. NADPH:adrenodoxin oxidoreductase Ferredoxin--NADP(+) reductase Adrenodoxin reductase Also acts on adrenodoxin. FAD 2 reduced ferredoxin + NADP(+) = 2 oxidized ferredoxin + NADPH. Ferredoxin--NAD(+) reductase Reduced ferredoxin + NAD(+) = oxidized ferredoxin + NADH. Dinucleotide phosphate reductase Rubredoxin--NAD(P)(+) reductase Rubredoxin--nicotinamide adenine dinucleotide (phosphate) reductase Rubredoxin--nicotinamide adenine NAD(P)H--rubredoxin oxidoreductase NAD(P)--rubredoxin oxidoreductase Ferredoxin is not utilized. FAD Reduced rubredoxin + NAD(P)(+) = oxidized rubredoxin + NAD(P)H. The enzyme reduces a number of electron carriers, including benzyl viologen, menadione and 2,6-dichloroindophenol, but rubredoxin is the most efficient. With dinitrogen as acceptor Nitrogenase Composed of two proteins that can be separated but are both required for nitrogenase activity. Acetylene is reduced to ethylene (but only very slowly to ethane), azide to nitrogen and ammonia, and cyanide to methane and ammonia. Dinitrogenase is a molybdenum-iron protein that reduces dinitrogen in three succesive two-electron reductions from nitrogen to diimine to hydrazine to two molecules of ammonia; the molybdenum may be replaced by vanadium or iron. Molybdenum or vanadium 8 reduced ferredoxin + 8 H(+) + N(2) + 16 ATP + 16 H(2)O = 8 oxidized ferredoxin + H(2) + 2 NH(3) + 16 ADP + 16 phosphate. Ferredoxin may be replaced by flavodoxin (see EC 1.19.6.1). Iron-sulfur The electron is transferred to the other protein, dinitrogenase (molybdoferredoxin). The reduction is initiated by formation of hydrogen in stoichiometric amounts. In the absence of a suitable substrate, hydrogen is slowly formed. Dinitrogen reductase is a [4Fe-4S] protein, which, with two molecules of ATP and ferredoxin, generates an electron. Acting on reduced flavodoxin as donor With dinitrogen as acceptor Nitrogenase (flavodoxin) Iron-sulfur 6 reduced flavodoxin + 6 H(+) + N(2) + n ATP = 6 oxidized flavodoxin + 2 NH(3) + n ADP + n phosphate. Molybdenum Acting on the aldehyde or oxo group of donors With NAD(+) or NADP(+) as acceptor Acylating acetaldehyde dehydrogenase Aldehyde dehydrogenase (acylating) Acetaldehyde dehydrogenase (acetylating) Acetaldehyde + CoA + NAD(+) = acetyl-CoA + NADH. It is the final enzyme in the meta-cleavage pathway for the degradation of phenols, cresols and catechol, converting the acetaldehyde produced by EC 4.1.3.39 into acetyl-CoA. NADP(+) can replace NAD(+) but the rate of reaction is much slower. Also acts, more slowly, on glycolaldehyde, propanal and butanal. In Pseudomonas species, this enzyme forms part of a bifunctional enzyme with EC 4.1.3.39. Aspartate-semialdehyde dehydrogenase ASA dehydrogenase L-aspartate-beta-semialdehyde dehydrogenase Aspartic semialdehyde dehydrogenase L-aspartate 4-semialdehyde + phosphate + NADP(+) = L-4-aspartyl phosphate + NADPH. Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) Triosephosphate dehydrogenase GAPDH NAD-dependent glyceraldehyde-3-phosphate dehydrogenase D-glyceraldehyde 3-phosphate + phosphate + NAD(+) = 3-phospho-D-glyceroyl phosphate + NADH. Also acts very slowly on D-glyceraldehyde and some other aldehydes. Thiols can replace phosphate. Glyceraldehyde-3-phosphate dehydrogenase (NADP(+)) (phosphorylating) Triosephosphate dehydrogenase (NADP(+)) Triosephosphate dehydrogenase (NADP+) NADP-dependent glyceraldehyde-3-phosphate dehydrogenase D-glyceraldehyde 3-phosphate + phosphate + NADP(+) = 3-phospho-D-glyceroyl phosphate + NADPH. Malonate-semialdehyde dehydrogenase 3-oxopropanoate + NAD(P)(+) + H(2)O = malonate + NAD(P)H. Succinate-semialdehyde dehydrogenase (NAD(P)(+)) Succinate semialdehyde + NAD(P)(+) + H(2)O = succinate + NAD(P)H. Glyoxylate dehydrogenase (acylating) Glyoxylate + CoA + NADP(+) = oxalyl-CoA + NADPH. Malonate-semialdehyde dehydrogenase (acetylating) 3-oxopropanoate + CoA + NAD(P)(+) = acetyl-CoA + CO(2) + NAD(P)H. 4-aminobutanal dehydrogenase ABALDH 1-pyrroline dehydrogenase Gamma-guanidinobutyraldehyde dehydrogenase Aminobutyraldehyde dehydrogenase As 1-pyrroline and 4-aminobutanal are in equilibrium and can be interconverted spontaneously, 1-pyrroline may act as the starting substrate. The enzyme from some species exhibits broad substrate specificity and has a marked preference for straight-chain aldehydes (up to 7 carbon atoms) as substrates. The plant enzyme also acts on 4-guanidinobutanal (cf. EC 1.2.1.54). 4-aminobutanal + NAD(+) + H(2)O = 4-aminobutanoate + NADH. Formate dehydrogenase Together with EC 1.12.1.2, forms a system previously known as formate hydrogenlyase. Formate + NAD(+) = CO(2) + NADH. Glutarate-semialdehyde dehydrogenase Glutarate semialdehyde + NAD(+) + H(2)O = glutarate + NADH. Glycolaldehyde dehydrogenase Glycolaldehyde + NAD(+) + H(2)O = glycolate + NADH. Lactaldehyde dehydrogenase (S)-lactaldehyde + NAD(+) + H(2)O = (S)-lactate + NADH. Alpha-ketoaldehyde dehydrogenase 2-oxoaldehyde dehydrogenase (NAD(+)) Methylglyoxal dehydrogenase A 2-oxoaldehyde + NAD(+) + H(2)O = a 2-oxo acid + NADH. Not identical with EC 1.2.1.49. Succinate-semialdehyde dehydrogenase http://purl.uniprot.org/mim/271980 Succinate semialdehyde + NAD(+) + H(2)O = succinate + NADH. 2-oxoisovalerate dehydrogenase (acylating) Also acts on (S)-3-methyl-2-oxopentanoate and 4-methyl-2-oxopentanoate. 3-methyl-2-oxobutanoate + CoA + NAD(+) = 2-methylpropanoyl-CoA + CO(2) + NADH. 2,5-dioxovalerate dehydrogenase 2,5-dioxopentanoate + NADP(+) + H(2)O = 2-oxoglutarate + NADPH. Methylmalonate-semialdehyde dehydrogenase (acylating) MMSA dehydrogenase MSDH http://purl.uniprot.org/mim/603178 2-methyl-3-oxopropanoate + CoA + H(2)O + NAD(+) = propanoyl-CoA + HCO(3)(-) + NADH. The reaction occurs in two steps with the decarboxylation process preceding CoA-binding. Bicarbonate rather than CO(2) is released as a final product. Also converts 3-oxopropanoate into acetyl-CoA. Benzaldehyde dehydrogenase (NAD(+)) Benzaldehyde + NAD(+) + H(2)O = benzoate + NADH. Aryl-aldehyde dehydrogenase Oxidizes a number of aromatic aldehydes, but not aliphatic aldehydes. An aromatic aldehyde + NAD(+) + H(2)O = an aromatic acid + NADH. Aldehyde dehydrogenase (NAD(+)) http://purl.uniprot.org/mim/270200 Wide specificity, including oxidation of D-glucuronolactone to D-glucarate. An aldehyde + NAD(+) + H(2)O = an acid + NADH. http://purl.uniprot.org/mim/100650 Aryl-aldehyde dehydrogenase (NADP(+)) An aromatic aldehyde + NADP(+) + AMP + diphosphate + H(2)O = an aromatic acid + NADPH + ATP. Aminoadipate semialdehyde dehydrogenase L-alpha-aminoadipate delta-semialdehyde oxidoreductase L-alpha-aminoadipate delta-semialdehyde:NAD oxidoreductase L-aminoadipate-semialdehyde dehydrogenase L-alpha-aminoadipate delta-semialdehyde:nicotinamide adenine dinucleotide oxidoreductase 2-aminoadipic semialdehyde dehydrogenase Alpha-aminoadipate reductase Alpha-aminoadipate-semialdehyde dehydrogenase 2-aminoadipate semialdehyde dehydrogenase L-2-aminoadipate 6-semialdehyde + NAD(P)(+) + H(2)O = L-2-aminoadipate + NAD(P)H. http://purl.uniprot.org/mim/266100 Aminomuconate-semialdehyde dehydrogenase 2-aminomuconate 6-semialdehyde + NAD(+) + H(2)O = 2-aminomuconate + NADH. Also acts on 2-hydroxymuconate semialdehyde. D-aldopantoate dehydrogenase (R)-dehydropantoate dehydrogenase (R)-4-dehydropantoate + NAD(+) + H(2)O = (R)-3,3-dimethylmalate + NADH. Retinal dehydrogenase FAD Acts on both the 11-trans-and 13-cis-forms of retinal. Retinal + NAD(+) + H(2)O = retinoate + NADH. N-acetyl-gamma-glutamyl-phosphate reductase NAGSA dehydrogenase N-acetyl-glutamate semialdehyde dehydrogenase N-acetyl-L-glutamate 5-semialdehyde + NADP(+) + phosphate = N-acetyl-5-glutamyl phosphate + NADPH. Phenylacetaldehyde dehydrogenase Phenylacetaldehyde + NAD(+) + H(2)O = phenylacetate + NADH. Aldehyde dehydrogenase (NADP(+)) An aldehyde + NADP(+) + H(2)O = an acid + NADPH. 3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase 3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-dehydrogenase 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-al + NAD(+) + H(2)O = 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-oate + NADH. Glutamyl-gamma-semialdehyde dehydrogenase Glutamate-5-semialdehyde dehydrogenase Gamma-glutamylphosphate reductase Beta-glutamylphosphate reductase L-glutamate 5-semialdehyde + phosphate + NADP(+) = L-glutamyl 5-phosphate + NADPH. Fatty acyl-CoA reductase Hexadecanal dehydrogenase (acylating) Hexadecanal + CoA + NAD(+) = hexadecanoyl-CoA + NADH. Also acts, more slowly, on octadecanoyl-CoA. Formate dehydrogenase (NADP(+)) Formate + NADP(+) = CO(2) + NADPH. Selenium Iron Tungsten Cinnamoyl-CoA reductase Cinnamaldehyde + CoA + NADP(+) = cinnamoyl-CoA + NADPH. Also acts on a number of substituted cinnamoyl esters of coenzyme A. 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase Does not act on unsubstituted aliphatic or aromatic aldehydes or glucose. NAD(+) can replace NADP(+), but with lower affinity. 4-carboxy-2-hydroxy-cis,cis-muconate 6-semialdehyde + NADP(+) = 4-carboxy-2-hydroxy-cis,cis-muconate + NADPH. Formaldehyde dehydrogenase Formaldehyde + NAD(+) + H(2)O = formate + NADH. 4-trimethylammoniobutyraldehyde dehydrogenase 4-trimethylammoniobutanal + NAD(+) + H(2)O = 4-trimethylammoniobutanoate + NADH. Long-chain-aldehyde dehydrogenase The best substrate is dodecylaldehyde. A long-chain aldehyde + NAD(+) + H(2)O = a long-chain acid anion + NADH. Methylglyoxal dehydrogenase Alpha-ketoaldehyde dehydrogenase 2-oxoaldehyde dehydrogenase (NADP(+)) A 2-oxoaldehyde + NADP(+) + H(2)O = a 2-oxo acid + NADPH. Not identical with EC 1.2.1.23. Aldehyde dehydrogenase (NAD(P)(+)) An aldehyde + NAD(P)(+) + H(2)O = an acid + NAD(P)H. Long-chain-fatty-acyl-CoA reductase Acyl-CoA reductase A long-chain aldehyde + CoA + NADP(+) = a long-chain acyl-CoA + NADPH. Together with EC 6.2.1.19 forms a fatty acid reductase system which produces the substrate of EC 1.14.14.3, thus being part of the bacterial luciferase system. Pyruvate dehydrogenase (NADP(+)) Pyruvate:NADP(+) oxidoreductase Pyruvate + CoA + NADP(+) = acetyl-CoA + CO(2) + NADPH. The Euglena enzyme can also use FAD or methyl viologen as acceptor, more slowly. Inhibited by oxygen. Oxoglutarate dehydrogenase (NADP(+)) 2-oxoglutarate + CoA + NADP(+) = succinyl-CoA + CO(2) + NADPH. The Euglena enzyme can also use NAD(+) as acceptor, but more slowly. 4-hydroxyphenylacetaldehyde dehydrogenase With EC 4.2.1.87, brings about the metabolism of octopamine in Pseudomonas. 4-hydroxyphenylacetaldehyde + NAD(+) + H(2)O = 4-hydroxyphenylacetate + NADH. Gamma-guanidinobutyraldehyde dehydrogenase Involved in the degradation of arginine in Pseudomonas putida (cf. EC 1.2.1.19). 4-guanidinobutanal + NAD(+) + H(2)O = 4-guanidinobutanoate + NADH. Butanal dehydrogenase Butanal + CoA + NAD(P)(+) = butanoyl-CoA + NAD(P)H. Also acts on acetaldehyde, but more slowly. Phenylglyoxylate dehydrogenase (acylating) FAD Also reduces viologen dyes. Phenylglyoxylate + NAD(+) + CoA-SH = benzoyl-S-CoA + CO(2) + NADH. Iron-sulfur 2-oxoisovalerate is oxidized at 15% of the rate for phenylglyoxylate. The enzyme from Azoarcus evansii is specific for phenylglyoxylate. Thiamine diphosphate Triosephosphate dehydrogenase (NAD(P)(+)) NAD(P)-dependent glyceraldehyde-3-phosphate dehydrogenase Triosephosphate dehydrogenase (NAD(P)) Glyceraldehyde-3-phosphate dehydrogenase (NAD(P)(+)) (phosphorylating) D-glyceraldehyde 3-phosphate + phosphate + NAD(P)(+) = 3-phospho-D-glyceroyl phosphate + NAD(P)H. NAD(+) and NADP(+) can be used as cofactors with similar efficiency, unlike EC 1.2.1.12 and EC 1.2.1.13, which are NAD(+)-and NADP(+)-dependent, respectively. 5-carboxymethyl-2-hydroxymuconic-semialdehyde dehydrogenase Carboxymethylhydroxymuconic semialdehyde dehydrogenase 5-carboxymethyl-2-hydroxymuconate semialdehyde + H(2)O + NAD(+) = 5-carboxymethyl-2-hydroxymuconate + NADH. Involved in the tyrosine degradation pathway in Arthrobacter sp. 4-hydroxymuconic-semialdehyde dehydrogenase Involved in the 4-nitrophenol degradation pathway. 4-hydroxymuconic semialdehyde + NAD(+) + H(2)O = maleylacetate + NADH. 4-formylbenzenesulfonate dehydrogenase 4-formylbenzenesulfonate + NAD(+) + H(2)O = 4-sulfobenzoate + NADH. Involved in the toluene-4-sulfonate degradation pathway. 6-oxohexanoate dehydrogenase Last step in the cyclohexanol degradation pathway in Acinetobacter sp. 6-oxohexanoate + NADP(+) + H(2)O = adipate + NADPH. 4-hydroxybenzaldehyde dehydrogenase p-hydroxybenzaldehyde dehydrogenase 4-hydroxybenzaldehyde + NAD(+) + H(2)O = 4-hydroxybenzoate + NADH. Involved in the toluene degradation pathway in Pseudomonas mendocina. Salicylaldehyde dehydrogenase Salicylaldehyde + NAD(+) + H(2)O = salicylate + NADH. Involved in the naphthalene degradation pathway in some bacteria. Mycothiol-dependent formaldehyde dehydrogenase NAD/factor-dependent formaldehyde dehydrogenase The S-formylmycothiol formed hydrolyzes to mycothiol and formate. Zinc Formaldehyde + mycothiol + NAD(+) = S-formylmycothiol + NADH. Vanillin dehydrogenase Vanillin + NAD(+) + H(2)O = vanillate + NADH. Coniferyl-aldehyde dehydrogenase Also oxidizes other aromatic aldehydes, but not aliphatic aldehydes. Coniferyl aldehyde + H(2)O + NAD(P)(+) = ferulate + NAD(P)H. Fluoroacetaldehyde dehydrogenase The enzyme from Streptomyces cattleya has a high affinity for fluoroacetate and glycolaldehyde but not for acetaldehyde. Fluoroacetaldehyde + NAD(+) + H(2)O = fluoroacetate + NADH. Benzaldehyde dehydrogenase (NADP(+)) Benzaldehyde + NADP(+) + H(2)O = benzoate + NADPH. Glutamyl-tRNA reductase However, in the alpha-proteobacteria EC 2.3.1.37 is used in an alternative route to produce the product 5-aminolevulinate from succinyl-CoA and glycine. Forms part of the pathway for the biosynthesis of 5-aminolevulinate from glutamate, known as the C5 pathway, which is used in most eubacteria, and in all archaebacteria, algae and plants. L-glutamate 1-semialdehyde + NADP(+) + tRNA(Glu) = L-glutamyl-tRNA(Glu) + NADPH. Although higher plants do not possess EC 2.3.1.37, the protistan Euglena gracilis possesses both the C5 pathway and EC 2.3.1.37. This route is found in the mitochondria of fungi and animals, organelles that are considered to be derived from an endosymbiotic alpha-proteobacterium. SGSD Succinylglutamic semialdehyde dehydrogenase N-succinylglutamate 5-semialdehyde dehydrogenase Succinylglutamate-semialdehyde dehydrogenase This is the fourth enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. N-succinyl-L-glutamate 5-semialdehyde + NAD(+) + H(2)O = N-succinyl-L-glutamate + NADH. The five enzymes involved in this pathway are EC 2.3.1.109, EC 3.5.3.23, EC 2.6.1.11, EC 1.2.1.71 and EC 3.5.1.96. E4P dehydrogenase E4PDH Erythrose-4-phosphate dehydrogenase Erythrose 4-phosphate dehydrogenase Forms part of the pyridoxal-5'-phosphate coenzyme biosynthesis pathway in Escherichia coli, along with EC 1.1.1.290, EC 2.6.1.52, EC 1.1.1.262, EC 2.6.99.2 and EC 1.4.3.5. Was originally thought to be an EC 1.2.1.12, but this has since been disproved, as glyceraldehyde 3-phosphate is not a substrate. D-erythrose 4-phosphate + NAD(+) + H(2)O = 4-phosphoerythronate + NADH. Betaine aldehyde oxidase BADH Betaine-aldehyde dehydrogenase Betaine aldehyde dehydrogenase Betaine aldehyde + NAD(+) + H(2)O = betaine + NADH. In plants, this reaction is catalyzed by EC 1.14.15.7, whereas in animals and many bacteria, it is catalyzed by either membrane-bound choline dehydrogenase (EC 1.1.99.1) or soluble choline oxidase (EC 1.1.3.17). In contrast, different enzymes are involved in the first reaction. In many bacteria, plants and animals, the osmoprotectant betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 and EC 2.1.1.157. This enzyme is involved in the second step and appears to be the same in plants, animals and bacteria. Triosephosphate dehydrogenase Glyceraldehyde-3-phosphate dehydrogenase (NADP(+)) D-glyceraldehyde 3-phosphate + NADP(+) + H(2)O = 3-phospho-D-glycerate + NADPH. With a cytochrome as acceptor Formate dehydrogenase (cytochrome) Formate + 2 ferricytochrome b1 = CO(2) + 2 ferrocytochrome b1 + 2 H(+). Pyruvic dehydrogenase Pyruvate dehydrogenase (cytochrome) Pyruvate dehydrogenase Pyruvate + ferricytochrome b1 + H(2)O = acetate + CO(2) + ferrocytochrome b1. Thiamine diphosphate Formate dehydrogenase (cytochrome c-553) Formate + ferricytochrome c-553 = CO(2) + ferrocytochrome c-553. Saccharomyces cerevisiae cytochrome c, ferricyanide and phenazine methosulfate can act as acceptors. Carbon monoxide:methylene blue oxidoreductase Carbon-monoxide dehydrogenase (cytochrome b-561) Carbon monoxide oxygenase (cytochrome b-561) Carbon monoxide oxidase Iron-sulfur Molybdopterin cytosine dinucleotide FAD Oxygen, methylene blue and iodonitrotetrazolium chloride can act as nonphysiological electron acceptors. CO + H(2)O + 2 ferricytochrome b-561 = CO(2) + 2 H(+) + 2 ferrocytochrome b-561. With oxygen as acceptor Aldehyde oxidase Quinoline oxidase May be identical with EC 1.2.3.11. Also oxidizes quinoline and pyridine derivatives. Molybdenum FAD An aldehyde + H(2)O + O(2) = a carboxylic acid + H(2)O(2). Iron-sulfur Retinene oxidase Retinal oxidase Retinal + O(2) + H(2)O = retinoate + H(2)O(2). May be the same as EC 1.2.3.1. 4-hydroxyphenylpyruvate oxidase Involved in tyrosine degradation pathway in Arthrobacter sp. 4-hydroxyphenylpyruvate + 0.5 O(2) = 4-hydroxyphenylacetate + CO(2). Abscisic-aldehyde oxidase AO-delta While abscisic aldehyde is the best substrate, the enzyme also acts with indole-3-aldehyde, 1-naphthaldehyde and benzaldehyde as substrates, but more slowly. Involved in the abscisic-acid biosynthesis pathway in plants, along with EC 1.1.1.288, EC 1.13.11.51 and EC 1.14.13.93. Abscisic aldehyde + H(2)O + O(2) = abscisate + H(2)O(2). Acts on both (+)-and (-)-abscisic aldehyde. Pyruvate oxidase Phosphate-dependent pyruvate oxidase Pyruvic oxidase Pyruvate + phosphate + O(2) = acetyl phosphate + CO(2) + H(2)O(2). Two reducing equivalents are transferred from the resonant carbanion/enamine forms of 2-hydroxyethyl-thiamine-diphosphate to the adjacent flavin cofactor, yielding 2-acetyl-thiamine diphosphate (AcThDP) and reduced flavin. FADH is reoxidized by O(2) to yield H(2)O(2) and FAD and AcThDP is cleaved phosphorolytically to acetyl phosphate and thiamine diphosphate. FAD Thiamine diphosphate Oxalate oxidase Oxalate + O(2) + 2 H(+) = 2 CO(2) + H(2)O(2). Manganese Glyoxylate oxidase Glyoxylate + H(2)O + O(2) = oxalate + H(2)O(2). Pyruvate oxidase (CoA-acetylating) FAD Pyruvate + CoA + O(2) = acetyl-CoA + CO(2) + H(2)O(2). May be identical with EC 1.2.7.1. IAAld oxidase Indole-3-acetaldehyde oxidase IAA oxidase Indoleacetaldehyde oxidase While (indol-3-yl)acetaldehyde is the preferred substrate, it also oxidizes indole-3-carbaldehyde and acetaldehyde, but more slowly. Has a preference for aldehydes having an indole-ring structure as substrate. FAD Isoform of EC 1.2.3.1. May play a role in plant hormone biosynthesis as its activity is higher in the auxin-overproducing mutant, super-root1, than in wild-type Arabidopsis thaliana. (Indol-3-yl)acetaldehyde + H(2)O + O(2) = (indol-3-yl)acetate + H(2)O(2). Heme Molybdenum Pyridoxal oxidase Molybdenum Pyridoxal + H(2)O + O(2) = 4-pyridoxate + H(2)O(2). Aryl-aldehyde oxidase An aromatic aldehyde + O(2) + H(2)O = an aromatic carboxylic acid + H(2)O(2). Acts on benzaldehyde, vanillin and a number of other aromatic aldehydes, but not on aliphatic aldehydes or sugars. With a disulfide as acceptor Pyruvic dehydrogenase Pyruvate dehydrogenase Pyruvate decarboxylase Pyruvic acid dehydrogenase Pyruvate dehydrogenase (acetyl-transferring) MtPDC (mitochondrial pyruvate dehydogenase complex) Pyruvate dehydrogenase (lipoamide) Pyruvate dehydrogenase complex Pyruvate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-acetylating) Thiamine diphosphate http://purl.uniprot.org/mim/312170 http://purl.uniprot.org/mim/179060 Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO(2). It is a component (in multiple copies) of the multienzyme pyruvate dehydrogenase complex in which it is bound to a core of molecules of EC 2.3.1.12, which also binds multiple copies of EC 1.8.1.4. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.12. OGDC Alpha-oxoglutarate dehydrogenase Ketoglutaric dehydrogenase Oxoglutarate dehydrogenase (succinyl-transferring) Oxoglutarate dehydrogenase (lipoamide) Oxoglutarate decarboxylase Alpha-ketoglutaric dehydrogenase 2-oxoglutarate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-succinylating) AKGDH Oxoglutarate dehydrogenase 2-oxoglutarate: lipoate oxidoreductase Alpha-ketoglutaric acid dehydrogenase Alpha-ketoglutarate dehydrogenase 2-ketoglutarate dehydrogenase 2-oxoglutarate dehydrogenase Thiamine diphosphate It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.61. http://purl.uniprot.org/mim/203740 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO(2). It is a component of the multienzyme 2-oxoglutarate dehydrogenase complex in which multiple copies of it are bound to a core of molecules of EC 2.3.1.61, which also binds multiple copies of EC 1.8.1.4. Branched-chain keto acid dehydrogenase Alpha-keto-alpha-methylvalerate dehydrogenase Dehydrogenase, 2-oxoisovalerate (lipoate) 2-oxoisocaproate dehydrogenase 3-methyl-2-oxobutanoate dehydrogenase (lipoamide) BCOAD Dehydrogenase, branched chain alpha-keto acid Branched-chain (-2-oxoacid) dehydrogenase (BCD) Branched-chain alpha-oxo acid dehydrogenase Alpha-ketoisocaproic-alpha-keto-alpha-methylvaleric dehydrogenase Branched-chain ketoacid dehydrogenase Alpha-ketoisocaproate dehydrogenase Branched-chain alpha-keto acid dehydrogenase 2-oxoisovalerate (lipoate) dehydrogenase Branched-chain 2-oxo acid dehydrogenase Branched-chain 2-keto acid dehydrogenase BCKDH Alpha-oxoisocaproate dehydrogenase Alpha-ketoisocaproic dehydrogenase Branched chain keto acid dehydrogenase 3-methyl-2-oxobutanoate:lipoamide oxidoreductase (decarboxylating and acceptor-2-methylpropanoylating) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) Alpha-ketoisovalerate dehydrogenase http://purl.uniprot.org/mim/248600 It is a component of the multienzyme 3-methyl-2-oxobutanoate dehydrogenase complex in which multiple copies of it are bound to a core of molecules of EC 2.3.1.168, which also binds multiple copies of EC 1.8.1.4. Thiamine diphosphate It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.168. 3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO(2). It acts not only on 3-methyl-2-oxobutanaoate, but also on 4-methyl-2-oxopentanoate and (S)-3-methyl-2-oxopentanoate, so that it acts on the 2-oxo acids that derive from the action of transaminases on valine, leucine and isoleucine. With an iron-sulfur protein as acceptor Pyruvate:ferredoxin oxidoreductase Pyruvate synthase Pyruvate synthetase Pyruvate oxidoreductase Pyruvic-ferredoxin oxidoreductase Pyruvate + CoA + 2 oxidized ferredoxin = acetyl-CoA + CO(2) + 2 reduced ferredoxin + 2 H(+). Thiamine diphosphate Iron-sulfur 2-oxobutyrate synthase 2-oxobutanoate + CoA + oxidized ferredoxin = propanoyl-CoA + CO(2) + reduced ferredoxin. KGOR Alpha-ketoglutarate-ferredoxin oxidoreductase Alpha-ketoglutarate synthase 2-ketoglutarate ferredoxin oxidoreductase 2-oxoglutarate synthase 2-oxoglutarate ferredoxin oxidoreductase Thiamine diphosphate 2-oxoglutarate + CoA + 2 oxidized ferredoxin = succinyl-CoA + CO(2) + 2 reduced ferredoxin. Highly specific for 2-oxoglutarate. This enzyme is one of four 2-oxoacid oxidoreductases that are differentiated by their abilities to oxidatively decarboxylate different 2-oxoacids and form their CoA derivatives (see also EC 1.2.7.1, EC 1.2.7.7 and EC 1.2.7.8). Iron-sulfur Carbon-monoxide dehydrogenase (ferredoxin) The enzyme from Moorella thermoacetica exists as a complex with EC 2.3.1.169, which catalyzes the overall reaction: methylcorrinoid protein + CoA + CO(2) + reduced ferredoxin = acetyl-CoA + corrinoid protein + H(2)O + oxidized ferredoxin. Zinc CO + H(2)O + oxidized ferredoxin = CO(2) + reduced ferredoxin. Methyl viologen can act as acceptor. Nickel Iron Tungsten-containing aldehyde ferredoxin oxidoreductase AOR Aldehyde ferredoxin oxidoreductase Can use ferredoxin or methyl viologen but not NAD(P)(+) as electron acceptor. This is an oxygen-sensitive enzyme. Tungsten-molybdopterin Iron-sulfur However, it does not oxidize glyceraldehyde 3-phosphate (see EC 1.2.7.6). Catalyzes the oxidation of aldehydes (including crotonaldehyde, acetaldehyde, formaldehyde and glyceraldehyde) to their corresponding acids. An aldehyde + H(2)O + 2 oxidized ferredoxin = an acid + 2 H(+) + 2 reduced ferredoxin. Glyceraldehyde-3-phosphate Fd oxidoreductase Glyceraldehyde-3-phosphate dehydrogenase (ferredoxin) Glyceraldehyde-3-phosphate ferredoxin reductase GAPOR Tungsten-molybdopterin Specific for glyceraldehyde-3-phosphate. Iron-sulfur Thought to function in place of glyceraldehyde-3-phosphate dehydrogenase and possibly phosphoglycerate kinase in the novel Embden-Meyerhof-type glycolytic pathway found in Pyrococcus furiosus. D-glyceraldehyde-3-phosphate + H(2)O + 2 oxidized ferredoxin = 3-phospho-D-glycerate + 2 H(+) + 2 reduced ferredoxin. Ketoisovalerate oxidoreductase 3-methyl-2-oxobutanoate dehydrogenase (ferredoxin) Branched-chain ketoacid ferredoxin reductase Ketoisovalerate ferredoxin reductase 3-methyl-2-oxobutanoate synthase (ferredoxin) Keto-valine-ferredoxin oxidoreductase Branched-chain oxo acid ferredoxin reductase 2-ketoisovalerate ferredoxin reductase 2-oxoisovalerate ferredoxin reductase VOR Iron-sulfur Tungsten-molybdopterin One of four 2-oxoacid oxidoreductases that are differentiated by their abilities to oxidatively decarboxylate different 2-oxoacids and form their CoA derivatives (see also EC 1.2.7.1, EC 1.2.7.3 and EC 1.2.7.8). Coenzyme-A 3-methyl-2-oxobutanoate + CoA + oxidized ferredoxin = S-(2-methylpropanoyl)-CoA + CO(2) + reduced ferredoxin. Preferentially utilizes 2-oxo-acid derivatives of branched chain amino acids, e.g. 3-methyl-2-oxopentanoate, 4-methyl-2-oxo-pentanoate, 2-oxobutyrate and 3-methylthiopropanamine. 3-(indol-3-yl)pyruvate synthase (ferredoxin) Indolepyruvate ferredoxin oxidoreductase IOR Thiamine diphosphate This enzyme, which is found in archaea, is one of four 2-oxoacid oxidoreductases that are differentiated by their abilities to oxidatively decarboxylate different 2-oxoacids and form their CoA derivatives (see also EC 1.2.7.1, EC 1.2.7.3 and EC 1.2.7.7). Preferentially utilizes the transaminated forms of aromatic amino acids and can use phenylpyruvate and 4-hydroxyphenylpyruvate as substrates. (Indol-3-yl)pyruvate + CoA + oxidized ferredoxin = S-2-(indol-3-yl)acetyl-CoA + CO(2) + reduced ferredoxin. Iron-sulfur With other acceptors Carbon monoxide oxygenase Carbon-monoxide dehydrogenase (acceptor) Carbon-monoxide dehydrogenase Anaerobic carbon monoxide dehydrogenase CO + H(2)O + A = CO(2) + AH(2). Forms part of a membrane-bound multienzyme complex with EC 1.12.99.6, which catalyzes the overall reaction: CO + H(2)O = CO(2) + H(2). Iron-sulfur Nickel It uses many electron acceptors, including ferredoxin, methyl viologen and benzyl viologen and flavins, but not pyridine nucleotides. Aldehyde dehydrogenase (pyrroloquinoline-quinone) Aldehyde dehydrogenase (acceptor) PQQ Wide specificity; acts on straight-chain aldehydes up to C(10), aromatic aldehydes, glyoxylate and glyceraldehyde. An aldehyde + acceptor + H(2)O = a carboxylate + reduced acceptor. Formaldehyde dismutase Formaldehyde and acetaldehyde can act as donors; formaldehyde, acetaldehyde and propanal can act as acceptors. 2 formaldehyde + H(2)O = formate + methanol. Formylmethanofuran dehydrogenase Methyl viologen can act as acceptor. Molybdenum Formylmethanofuran + H(2)O + acceptor = CO(2) + methanofuran + reduced acceptor. Also oxidizes N-furfurylformamide. Carboxylate reductase Methyl viologen can act as acceptor. In the reverse direction, non-activated acids are reduced by reduced viologens to aldehydes, but not to the corresponding alcohols. Tungsten An aldehyde + acceptor + H(2)O = a carboxylate + reduced acceptor. AORDd Aldehyde oxidoreductase Aldehyde dehydrogenase (FAD-independent) Aldehyde oxidase Molybdopterin cytosine dinucleotide An aldehyde + H(2)O + acceptor = a carboxylate + reduced acceptor. Iron-sulfur Acting on phosphorus or arsenic in donors Acting on phosphorus or arsenic in donors, with NAD(P)(+) as acceptor Phosphite dehydrogenase Phosphonate dehydrogenase NAD-dependent phosphite dehydrogenas NAD:phosphite oxidoreductase NADP(+) is a poor substitute for NAD(+) in the enzyme from Pseudomonas stutzeri WM88. Phosphonate + NAD(+) + H(2)O = phosphate + NADH. Acting on phosphorus or arsenic in donors, with disulfide as acceptor Arsenate reductase (glutaredoxin) Although the arsenite formed is more toxic than arsenate, it can be extruded from some bacteria by EC 3.6.3.16. Molybdenum Thioredoxins reduced by NADPH and thioredoxin reductase can act as alternative substrates. Arsenate + glutaredoxin = arsenite + glutaredoxin disulfide + H(2)O. The glutaredoxins catalyze glutathione-disulfide oxidoreductions and have a redox-active disulfide/dithiol in the active site (-Cys-Pro-Tyr-Cys-) that forms a disulfide bond in the oxidized form. The enzyme is part of a system for detoxifying arsenate. Glutaredoxins have a binding site for glutathione, which is required to reduce them to the dithiol form. In other organisms, arsenite can be methylated by EC 2.1.1.137 in a pathway to non-toxic organoarsenical compounds. MMA(V) reductase Methylarsonate reductase Methylarsonate + 2 glutathione = methylarsonite + glutathione disulfide + H(2)O. The product, Me-As(OH)(2) (methylarsonous acid), is biologically methylated by EC 2.1.1.137 to form cacodylic acid (dimethylarsinic acid). Acting on phosphorus or arsenic in donors, with other, known acceptors Arsenite oxidase Arsenate reductase (azurin) Iron-sulfur Molybdenum Molybdopterin The enzyme also uses a c-type cytochrome or O(2) as acceptors. Arsenite + H(2)O + 2 azurin(ox) = arsenate + 2 azurin(red) + 2 H(+). Acting on phosphorus or arsenic in donors, with other acceptors Arsenate reductase (donor) Unlike EC 1.20.4.1 reduced glutaredoxin cannot serve as a reductant. Arsenite + acceptor = arsenate + reduced acceptor. Benzyl viologen can act as an acceptor. Acting on x-H and y-H to form an x-y bond With oxygen as acceptor Isopenicillin-N synthase Forms part of the penicillin biosynthesis pathway. N-((5S)-5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine + O(2) = isopenicillin N + 2 H(2)O. Berberine synthase Columbamine oxidase Iron 2 columbamine + O(2) = 2 berberine + 2 H(2)O. Oxidation of the O-methoxyphenol structure forms the methylenedioxy group of berberine. Reticuline oxidase Berberine-bridge-forming enzyme Tetrahydroprotoberberine synthase Berberine bridge enzyme The product of the reaction, (S)-scoulerine, is a precursor of protopine, protoberberine and benzophenanthridine alkaloid biosynthesis in plants. FAD (S)-reticuline + O(2) = (S)-scoulerine + H(2)O(2). Acts on (S)-reticuline and related compounds, converting the N-methyl group into the methylene bridge ('berberine bridge') of (S)-tetrahydroprotoberberines. Sulochrin oxidase Sulochrin oxidase ((+)-bisdechlorogeodin-forming) Involved in the biosynthesis of mold metabolites related to the antibiotic griseofulvin. Also acts on several diphenols and phenylenediamines, but has low affinity for these substrates. 2 sulochrin + O(2) = 2 (+)-bisdechlorogeodin + 2 H(2)O. Sulochrin oxidase Sulochrin oxidase ((-)-bisdechlorogeodin-forming) Involved in the biosynthesis of mold metabolites related to the antibiotic griseofulvin. 2 sulochrin + O(2) = 2 (-)-bisdechlorogeodin + 2 H(2)O. Also acts on several diphenols and phenylenediamines, but has low affinity for these substrates. Aureusidin synthase Plays a key role in the yellow coloration of flowers such as snapdragon. Copper (1) 2',4,4',6'-tetrahydroxychalcone + O(2) = aureusidin + H(2)O. The enzyme is a homolog of plant polyphenol oxidase and catalyzes two separate chemical transformations, i.e. 3-hydroxylation and oxidative cyclization (2',alpha-dehydrogenation). (2) 2',3,4,4',6'-pentahydroxychalcone + 0.5 O(2) = aureusidin + H(2)O. H(2)O(2) activates reaction (1) but inhibits reaction (2). With a disulfide as acceptor D-proline reductase (dithiol) 5-aminopentanoate + lipoate = D-proline + dihydrolipoate. Other dithiols can function as reducing agents; the enzyme contains a pyruvoyl group and a selenocysteine residue, both essential for activity. Pyruvate The reaction is observed only in the direction of D-proline reduction. Glycine reductase Only subunit B distinguishes this enzyme from EC 1.21.4.3 and EC 1.21.4.4. The enzyme from Eubacterium acidaminophilum consists of subunits A, B and C. The reaction is observed only in the direction of glycine reduction. Subunit A, which also contains selenocysteine, is reduced by thioredoxin, and is needed to convert the carboxymethyl group into a ketene equivalent, in turn used by subunit C to produce acetyl phosphate. Subunit B contains selenocysteine and a pyruvoyl group, and is responsible for glycine binding and ammonia release. Acetyl phosphate + NH(3) + thioredoxin disulfide + H(2)O = glycine + phosphate + thioredoxin. Sarcosine reductase Only subunit B distinguishes this enzyme from EC 1.21.4.2 and EC 1.21.4.4. Subunit B contains selenocysteine and a pyruvoyl group, and is responsible for sarcosine binding and methylamine release. Acetyl phosphate + methylamine + thioredoxin disulfide = N-methylglycine + phosphate + thioredoxin. The reaction is observed only in the direction of sarcosine reduction. Subunit A, which also contains selenocysteine, is reduced by thioredoxin, and is needed to convert the carboxymethyl group into a ketene equivalent, in turn used by subunit C to produce acetyl phosphate. The enzyme from Eubacterium acidaminophilum consists of subunits A, B and C. Betaine reductase Only subunit B distinguishes this enzyme from EC 1.21.4.2 and EC 1.21.4.3. The reaction is observed only in the direction of betaine reduction. The enzyme from Eubacterium acidaminophilum consists of subunits A, B and C. Acetyl phosphate + trimethylamine + thioredoxin disulfide = N,N,N-trimethylglycine + phosphate + thioredoxin. Subunit B contains selenocysteine and a pyruvoyl group, and is responsible for glycine binding and ammonia release. Subunit A, which also contains selenocysteine, is reduced by thioredoxin, and is needed to convert the carboxymethyl group into a ketene equivalent, in turn used by subunit C to produce acetyl phosphate. With other acceptors Beta-cyclopiazonic oxidocyclase Beta-cyclopiazonate dehydrogenase Beta-cyclopiazonate oxidocyclase FAD Cytochrome c and various dyes can act as acceptor. Beta-cyclopiazonate + acceptor = alpha-cyclopiazonate + reduced acceptor. Cyclopiazonate is a microbial toxin. Acting on the CH-CH group of donors With NAD(+) or NADP(+) as acceptor Dihydrouracil dehydrogenase (NAD(+)) 5,6-dihydrouracil + NAD(+) = uracil + NADH. Enoyl acyl-carrier-protein reductase Enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific) Acyl-ACP dehydrogenase Enoyl-ACP reductase NADPH 2-enoyl Co A reductase Acyl-[acyl-carrier-protein] + NADP(+) = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADPH. The Saccharomyces cerevisiae and Escherichia coli enzymes are B-specific with respect to NADP(+) (cf. EC 1.3.1.9). Catalyzes the reduction of enoyl-acyl-[acyl-carrier-protein] derivatives of carbon chain length from 4 to 16. Melilotate dehydrogenase 2-coumarate reductase 3-(2-hydroxyphenyl)propanoate + NAD(+) = 2-coumarate + NADH. Hydroxyphenylpyruvate synthase Prephenate dehydrogenase Chorismate mutase--prephenate dehydrogenase Prephenate + NAD(+) = 4-hydroxyphenylpyruvate + CO(2) + NADH. This enzyme in the enteric bacteria also possesses EC 5.4.99.5 activity and converts chorismate into prephenate. Prephenate dehydrogenase (NADP(+)) Prephenate + NADP(+) = 4-hydroxyphenylpyruvate + CO(2) + NADPH. Orotate reductase (NADH) FMN (S)-dihydroorotate + NAD(+) = orotate + NADH. FAD Orotate reductase (NADPH) Flavoprotein (S)-dihydroorotate + NADP(+) = orotate + NADPH. Beta-nitroacrylate reductase 3-nitropropanoate + NADP(+) = 3-nitroacrylate + NADPH. 3-methyleneoxindole reductase 3-methyl-1,3-dihydroindol-2-one + NADP(+) = 3-methylene-1,3-dihydro-2H-indol-2-one + NADPH. Kynurenate-7,8-dihydrodiol dehydrogenase 7,8-dihydro-7,8-dihydroxykynurenate + NAD(+) = 7,8-dihydroxykynurenate + NADH. Cis-1,2-dihydrobenzene-1,2-diol dehydrogenase Cis-benzene glycol dehydrogenase Cis-1,2-dihydrobenzene-1,2-diol + NAD(+) = catechol + NADH. Dihydrothymine dehydrogenase Dihydropyrimidine dehydrogenase (NADP(+)) Dihydrouracil dehydrogenase (NADP+) 5,6-dihydrouracil + NADP(+) = uracil + NADPH. Also acts on dihydrothymine. http://purl.uniprot.org/mim/274270 Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol + NADPH. 7-dehydrocholesterol reductase Sterol Delta(7)-reductase 7-DHC reductase http://purl.uniprot.org/mim/270400 http://purl.uniprot.org/mim/268670 Cholesterol + NADP(+) = cholesta-5,7-dien-3-beta-ol + NADPH. Cholestenone 5-alpha-reductase 5-alpha-cholestan-3-one + NADP(+) = cholest-4-en-3-one + NADPH. Biliverdin reductase Bilirubin + NAD(P)(+) = biliverdin + NAD(P)H. 3,5-cyclohexadiene-1,2-diol-1-carboxylate dehydrogenase Cis-1,2-dihydroxycyclohexa-3,5-diene-1-carboxylate dehydrogenase 2-hydro-1,2-dihydroxybenzoate dehydrogenase 3,5-cyclohexadiene-1,2-diol-1-carboxylic acid dehydrogenase 1,6-dihydroxycyclohexa-2,4-diene-1-carboxylate dehydrogenase Dihydrodihydroxybenzoate dehydrogenase DHB dehydrogenase Cis-1,2-dihydroxycyclohexa-3,5-diene-1-carboxylate:NAD(+) oxidoreductase DHBDH (1R,6R)-1,6-dihydroxycyclohexa-2,4-diene-1-carboxylate + NAD(+) = catechol + CO(2) + NADH. Dihydrodipicolinate reductase 2,3,4,5-tetrahydrodipicolinate + NAD(P)(+) = 2,3-dihydrodipicolinate + NAD(P)H. 2-hexadecenal reductase 2-alkenal reductase Hexadecanal + NADP(+) = 2-trans-hexadecenal + NADPH. Specific for long chain 2-trans-and 2-cis-alkenals, with chain length optimum around 14 to 16 carbon atoms. 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase 2,3-DHB dehydrogenase 2,3-dihydro-2,3-dihydroxybenzoate + NAD(+) = 2,3-dihydroxybenzoate + NADH. Cis-dihydrodiol naphthalene dehydrogenase Cis-1,2-dihydro-1,2-dihydroxynaphthalene dehydrogenase Cis-naphthalene dihydrodiol dehydrogenase Cis-1,2-dihydronaphthalene-1,2-diol + NAD(+) = naphthalene-1,2-diol + NADH. Also acts, at half the rate, on cis-anthracene dihydrodiol and cis-phenanthrene dihydrodiol. Delta(4)-3-ketosteroid 5-beta-reductase Delta(4)-hydrogenase 3-oxo-Delta(4)-steroid 5-beta-reductase 5-beta-reductase Delta(4)-5-beta-reductase Cholestenone 5-beta-reductase Testosterone 5-beta-reductase Androstenedione 5-beta-reductase Cortisone 5-beta-reductase Steroid 5-beta-reductase Cortisone beta-reductase Delta(4)-3-oxosteroid 5-beta-reductase Cortisone Delta(4)-5-beta-reductase http://purl.uniprot.org/mim/235555 The bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one can also act as substrates. (2) 17,21-dihydroxy-5-beta-pregnane-3,11,20-trione + NADP(+) = cortisone + NADPH. (1) 5-beta-cholestan-3-one + NADP(+) = cholest-4-en-3-one + NADPH. The enzyme from human efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites; it can also act on aldosterone, corticosterone and cortisol, but to a lesser extent. Steroid 5-alpha-reductase Progesterone 5-alpha-reductase 5-alpha-pregnan-3,20-dione + NADP(+) = progesterone + NADPH. Testosterone and 20-alpha-hydroxy-4-pregn-3-one can act in place of progesterone. Enoate reductase 2-enoate reductase Acts, in the reverse direction, on a wide range of alkyl and aryl alpha-beta-unsaturated carboxylate ions; 2-butenoate was the best substrate tested. Iron-sulfur FAD Butanoate + NAD(+) = 2-butenoate + NADH. Maleolylacetate reductase Maleylacetate reductase 3-oxoadipate + NAD(P)(+) = 2-maleylacetate + NAD(P)H. Protochlorophyllide oxidoreductase Protochlorophyllide reductase NADPH-protochlorophyllide oxidoreductase Catalyzes a light-dependent trans-reduction of the D-ring of protochlorophyllide; the product has the (7S,8S)-configuration. Chlorophyllide a + NADP(+) = protochlorophyllide + NADPH. 2,4-dienoyl-CoA reductase (NADPH) 4-enoyl-CoA reductase (NADPH) Trans-2,3-didehydroacyl-CoA + NADP(+) = trans,trans-2,3,4,5-tetradehydroacyl-CoA + NADPH. http://purl.uniprot.org/mim/222745 Best substrates for reduction contain a 2,4-diene structure with chain length C(8) or C(10). Phosphatidylcholine desaturase Linoleate synthase Oleate desaturase Oleoyl-CoA desaturase 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine + NAD(+) = 1-acyl-2-linoleoyl-sn-glycero-3-phosphocholine + NADH. Also desaturates phosphatidylcholine containing the oleoyl group on O-2 of the glycerol residue. Geissoschizine dehydrogenase Involved in the interconversion of heteroyohimbine alkaloids in Catharanthus roseus. Geissoschizine + NADP(+) = 4,21-dehydrogeissoschizine + NADPH. Cis-2-enoyl-CoA reductase (NADPH) Acyl-CoA + NADP(+) = cis-2,3-dehydroacyl-CoA + NADPH. Not identical with EC 1.3.1.38 (cf. EC 1.3.1.8). Trans-2-enoyl-CoA reductase (NADPH) Acyl-CoA + NADP(+) = trans-2,3-dehydroacyl-CoA + NADPH. Not identical with EC 1.3.1.37 (cf. EC 1.3.1.8). Enoyl-[acyl-carrier-protein] reductase (NADPH, A-specific) Acyl-ACP dehydrogenase The liver enzyme is A-specific with respect to NADP(+) (cf. EC 1.3.1.10). Acyl-[acyl-carrier-protein] + NADP(+) = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADPH. Cortisone alpha-reductase 4,5-alpha-dihydrocortisone + NADP(+) = cortisone + NADPH. 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate reductase Broad specificity; reduces a number of compounds produced by Pseudomonas from aromatic hydrocarbons by ring fission. 2,6-dioxo-6-phenylhexanoate + NADP(+) = 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate + NADPH. Xanthommatin reductase 5,12-dihydroxanthommatin + NAD(+) = xanthommatin + NADH. From Drosophila melanogaster. 12-oxophytodienoate reductase Involved in the conversion of linolenate into jasmonate in Zea mays. 8-((1R,2R)-3-oxo-2-((Z)-pent-2-enyl)cyclopentyl)octanoate + NADP(+) = (15Z)-12-oxophyto-10,15-dienoate + NADPH. Cyclohexadienyl dehydrogenase Arogenic dehydrogenase Arogenate dehydrogenase Pretyrosine dehydrogenase L-arogenate:NAD(+) oxidoreductase See also EC 1.3.1.12, EC 1.3.1.78 and EC 1.3.1.79. L-arogenate + NAD(+) = L-tyrosine + NADH + CO(2). Trans-2-enoyl-CoA reductase (NAD(+)) Acyl-CoA + NAD(+) = trans-didehydroacyl-CoA + NADH. The enzyme from Euglena gracilis acts on crotonoyl-CoA and, more slowly, on trans-hex-2-enoyl-CoA and trans-oct-2-enoyl-CoA. 2'-hydroxyisoflavone reductase Vestitone + NADP(+) = 2'-hydroxyformononetin + NADPH. Involved in the biosynthesis of the pterocarpin phytoalexins medicarpin and maackiain. In the reverse reaction, a 2'-hydroxyisoflavone is reduced to an isoflavanone; 2'-hydroxypseudobaptigenin also acts. Biochanin-A reductase Dihydrobiochanin A + NADP(+) = biochanin A + NADPH. Some other isoflavones are reduced to the corresponding isoflavanones. Alpha-santonin 1,2-reductase 1,2-dihydrosantonin + NAD(P)(+) = alpha-santonin + NAD(P)H. 15-oxoprostaglandin 13-oxidase (5Z)-(15S)-11-alpha-hydroxy-9,15-dioxoprostanoate + NAD(P)(+) = (5Z)-(15S)-11-alpha-hydroxy-9,15-dioxoprosta-13-enoate + NAD(P)H. The enzyme from placenta is specific for NAD(+). Reduces 15-oxoprostaglandins to 13,14-dihydro derivatives. Cis-3,4-dihydrophenanthrene-3,4-diol dehydrogenase (+)-cis-3,4-dihydrophenanthrene-3,4-diol + NAD(+) = phenanthrene-3,4-diol + NADH. Cucurbitacin Delta(23)-reductase Manganese 23,24-dihydrocucurbitacin + NAD(P)(+) = cucurbitacin + NAD(P)H. Iron or zinc can replace manganese to some extent. Cucurbitacin is a plant triterpenoid. HDR NADPH:2'-hydroxydaidzein oxidoreductase 2'-hydroxydihydrodaidzein:NADP(+) 2'-oxidoreductase 2'-hydroxydaidzein reductase Also acts on 2'-hydroxyformononetin and to a small extent on 2'-hydroxygenistein. In the reverse reaction, the 2'-hydroxyisoflavone (2'-hydroxydaidzein) is reduced to an isoflavanone. 2'-hydroxy-2,3-dihydrodaidzein + NADP(+) = 2'-hydroxydaidzein + NADPH. The isoflavones biochanin A, daidzein and genestein as well as the flavonoids apigenin, kaempferol and quercetin do not act as substrates. Involved in the biosynthesis of the phytoalexin glyceollin. 2-methyl-branched-chain-enoyl-CoA reductase FAD From Ascaris suum. The reaction proceeds only in the presence of another flavoprotein ('electron-transferring flavoprotein'). 2-methylbutanoyl-CoA + NAD(+) = 2-methylcrotonoyl-CoA + NADH. (1R,2S)-dihydroxy-3,5-cyclohexadiene-1,4-dicarboxylate dehydrogenase (3S,4R)-3,4-dihydroxycyclohexa-1,5-diene-1,4-dicarboxylate dehydrogenase Dihydroxy-3,5-cyclohexadiene-1,4-dicarboxylate dehydrogenase Iron (3S,4R)-3,4-dihydroxycyclohexa-1,5-diene-1,4-dicarboxylate + NAD(+) = 3,4-dihydroxybenzoate + CO(2) + NADH. Precorrin-6X reductase Precorrin-6Y:NADP(+) oxidoreductase Precorrin-6A reductase Precorrin-6B + NADP(+) = precorrin-6A + NADPH. Biphenyl-2,3-dihydro-2,3-diol dehydrogenase 2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase Cis-2,3-dihydrobiphenyl-2,3-diol dehydrogenase Catalyzes the second step in the biphenyl degradation pathway in bacteria. Cis-3-phenylcyclohexa-3,5-diene-1,2-diol + NAD(+) = biphenyl-2,3-diol + NADH. Phloroglucinol reductase Involved in the gallate anaerobic degradation pathway in bacteria. Dihydrophloroglucinol + NADP(+) = phloroglucinol + NADPH. 2,3-dihydroxy-2,3-dihydro-p-cumate dehydrogenase Biphenyl-2,3-dihydro-2,3-diol dehydrogenase Involved in the p-cymene and p-cumate degradation pathways in Pseudomonas putida. Cis-5,6-dihydroxy-4-isopropylcyclohexa-1,3-dienecarboxylate + NAD(+) = 2,3-dihydroxy-p-cumate + NADH. Fumarate reductase (NADH) NADH-dependent fumarate reductase Succinate + NAD(+) = fumarate + NADH. Dibenzothiophene dihydrodiol dehydrogenase Involved in the dibenzothiophene degradation pathway in bacteria. Cis-1,2-dihydroxy-1,2-dihydrodibenzothiophene + NAD(+) = 1,2-dihydroxydibenzothiophene + NADH. Terephthalate 1,2-cis-dihydrodiol dehydrogenase Cis-4,5-dihydroxycyclohexa-1(6),2-diene-1,4-dicarboxylate + NAD(+) = 3,4-dihydroxybenzoate + CO(2) + NADH. Involved in the terephthalate degradation pathway in bacteria. Pimeloyl-CoA dehydrogenase Pimeloyl-CoA + NAD(+) = 6-carboxyhex-2-enoyl-CoA + NADH. Involved in the benzoate degradation (anaerobic) pathway in bacteria. 2,4-dichlorobenzoyl-CoA reductase 4-chlorobenzoyl-CoA + NADP(+) + HCl = 2,4-dichlorobenzoyl-CoA + NADPH. Acts in the reverse direction to form part of the 2,4-dichlorobenzoate degradation pathway in bacteria. Phthalate 4,5-cis-dihydrodiol dehydrogenase Involved in the phthalate degradation pathway in bacteria. Cis-4,5-dihydroxycyclohexa-1(6),2-diene-1,2-dicarboxylate + NAD(+) = 4,5-dihydroxyphthalate + NADH. 5,6-dihydroxy-3-methyl-2-oxo-1,2,5,6-tetrahydroquinoline dehydrogenase Acts in the reverse direction to form part of the 3-methylquinoline degradation pathway in bacteria. 5,6-dihydroxy-3-methyl-2-oxo-1,2,5,6-tetrahydroquinoline + NAD(+) = 5,6-dihydroxy-3-methyl-2-oxo-1,2-dihydroquinoline + NADH. Cis-dihydroethylcatechol dehydrogenase Cis-1,2-dihydro-3-ethylcatechol + NAD(+) = 3-ethylcatechol + NADH. Involved in the ethylbenzene degradation pathway in bacteria. Cis-1,2-dihydroxy-4-methylcyclohexa-3,5-diene-1-carboxylate dehydrogenase Cis-1,2-dihydroxy-4-methylcyclohexa-3,5-diene-1-carboxylate + NAD(P)(+) = 4-methylcatechol + NAD(P)H + CO(2). Involved in the p-xylene degradation pathway in bacteria. 1,2-dihydroxy-6-methylcyclohexa-3,5-dienecarboxylate dehydrogenase Involved in the o-xylene degradation pathway in bacteria. 1,2-dihydroxy-6-methylcyclohexa-3,5-dienecarboxylate + NAD(+) = 3-methylcatechol + NADH + CO(2). Zeatin reductase Dihydrozeatin + NADP(+) = zeatin + NADPH. Previously classified erroneously as EC 1.1.1.242. Meso-tartrate dehydrogenase Meso-tartrate + NAD(+) = dihydroxyfumarate + NADH. C-14 sterol reductase Sterol C14-reductase Delta(14)-sterol reductase 4,4-dimethyl-5-alpha-cholesta-8,24-dien-3-beta-ol + NADP(+) = 4,4-dimethyl-5-alpha-cholesta-8,14,24-trien-3-beta-ol + NADPH. http://purl.uniprot.org/mim/215140 Acts on a range of steroids with a 14(15)-double bond. Delta(24(24(1)))-sterol reductase C-24(28) sterol reductase Sterol Delta(24(28))-reductase Sterol Delta(24(28))-methylene reductase Ergosterol + NADP(+) = ergosta-5,7,22,24(24(1))-tetraen-3-beta-ol + NADPH. Acts on a range of steroids with a 24(24(1))-double bond. Delta(24)-sterol reductase Lanosterol Delta(24)-reductase 5-alpha-cholest-7-en-3-beta-ol + NADP(+) = 5-alpha-cholesta-7,24-dien-3-beta-ol + NADPH. Acts on a range of steroids with a 24(25)-double bond, including lanosterol, desmosterol and zymosterol. 1,2-dihydrovomilenine reductase 17-O-acetylnorajmaline + NADP(+) = 1,2-dihydrovomilenine + NADPH. Forms part of the ajmaline biosynthesis pathway. 2-alkenal reductase NAD(P)H-dependent alkenal/one oxidoreductase NADPH:2-alkenal alpha,beta-hydrogenase Exhibits high activities also for 2-alkenones such as but-3-en-2-one and pent-3-en-2-one. Inactive with cyclohex-2-en-1-one and 12-oxophytodienoic acid. Highly specific for 4-hydroxy-non-2-enal and non-2-enal. Involved in the detoxification of alpha,beta-unsaturated aldehydes and ketones. 2-alkenals of shorter chain have lower affinities. n-alkanal + NAD(P)(+) = alk-2-enal + NAD(P)H. [4-vinyl]chlorophyllide a reductase 4VCR Divinyl chlorophyllide a 8-vinyl-reductase Chlorophyllide a + NADP(+) = divinyl chlorophyllide a + NADPH. Also reduces divinyl protochlorophyllide to protochlorophyllide in some species, providing an alternative pathway. Precorrin-2 dehydrogenase Precorrin-2 oxidase Catalyzes the second of three steps leading to the formation of siroheme from uroporphyrinogen III. The first step involves the donation of two S-adenosyl-L-methionine-derived methyl groups to carbons 2 and 7 of uroporphyrinogen III to form precorrin-2 (EC 2.1.1.107) and the third step involves the chelation of ferrous iron to sirohydrochlorin to form siroheme (EC 4.99.1.4). In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. In some bacteria, steps 1-3 are catalyzed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirC being responsible for the above reaction. Precorrin-2 + NAD(+) = sirohydrochlorin + NADH. ANR Anthocyanidin reductase Forms 2,3-cis-flavan-3-ols. Also, while the substrate preference of MtANR is cyanidin>pelargonidin>delphinidin, the reverse preference is found with AtANR. While the enzyme from the legume Medicago truncatula (MtANR) uses both NADPH and NADH as reductant, that from the crucifer Arabidopsis thaliana (AtANR) uses only NADPH. A flavan-3-ol + 2 NAD(P)(+) = an anthocyanidin + 2 NAD(P)H. The isomeric 2,3-trans-flavan-3-ols are formed from flavan-3,4-diols by EC 1.17.1.3. TyrAAT1 TyrAAT2 Pretyrosine dehydrogenase TyrA(a) Arogenate dehydrogenase (NADP(+)) Arogenic dehydrogenase The enzyme from Synechocystis sp. PCC 6803 and the isoform TyrAAT1 cannot use prephenate as a substrate, while the isoform TyrAAT2 can use it only very poorly. L-arogenate + NADP(+) = L-tyrosine + NADPH + CO(2). Unlike EC 1.3.1.43 and EC 1.3.1.79, this enzyme has a strict requirement for NADP(+). Arogenic dehydrogenase Cyclohexadienyl dehydrogenase Pretyrosine dehydrogenase Arogenate dehydrogenase (NAD(P)(+)) See also EC 1.3.1.12, EC 1.3.1.43 and EC 1.3.1.78. L-arogenate + NAD(P)(+) = L-tyrosine + NAD(P)H + CO(2). Enoyl coenzyme A reductase 2-enoyl-CoA reductase Acyl-CoA dehydrogenase (NADP(+)) The liver enzyme acts on enoyl-CoA derivatives of carbon chain length 4 to 16, with optimum activity on 2-hexenoyl-CoA. Acyl-CoA + NADP(+) = 2,3-dehydroacyl-CoA + NADPH. In Escherichia coli, cis-specific and trans-specific enzymes exist (cf. EC 1.3.1.37 and EC 1.3.1.38). NADH-specific enoyl-ACP reductase Enoyl-ACP reductase NADH-enoyl acyl carrier protein reductase Enoyl-[acyl-carrier-protein] reductase (NADH) Acyl-[acyl-carrier-protein] + NAD(+) = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADH. Catalyzes the reduction of enoyl-acyl-[acyl-carrier-protein] derivatives of carbon chain length from 4 to 16. With a cytochrome as acceptor GLDHase L-galactono-gamma-lactone dehydrogenase Galactonolactone dehydrogenase L-galactonolactone dehydrogenase GLDase Very specific for its substrate L-galactono-1,4-lactone as D-galactono-gamma-lactone, D-gulono-gamma-lactone, L-gulono-gamma-lactone, D-erythronic-gamma-lactone, D-xylonic-gamma-lactone, L-mannono-gamma-lactone, D-galactonate, D-glucuronate and D-gluconate are not substrates. (2) L-ascorbate + 2 ferricytochrome c = L-dehydroascorbate + 2 ferrocytochrome c + 2 H(+). (1) L-galactono-1,4-lactone + 2 ferricytochrome c = L-ascorbate + 2 ferrocytochrome c + 2 H(+). FAD, NAD(+), NADP(+) and O(2) (cf. EC 1.3.3.12) cannot act as electron acceptor. Catalyzes the final step in the biosynthesis of L-ascorbic acid in higher plants and in nearly all higher animals with the exception of primates and some birds. With oxygen as acceptor Dihydoorotic acid dehydrogenase DHOdehase Dihydroorotate oxidase Dihydroorotate dehydrogenase FMN Ferricyanide can act as acceptor. (S)-dihydroorotate + O(2) = orotate + H(2)O(2). FAD L-tryptophan 2',3'-oxidase Tryptophan alpha,beta-oxidase L-tryptophan alpha,beta-dehydrogenase L-tryptophan + O(2) = alpha,beta-didehydrotryptophan + H(2)O(2). Heme The product of the reaction can hydrolyze spontaneously to form indolepyruvate. Also catalyzes the alpha,beta dehydrogenation of L-tryptophan side chains in peptides. The enzyme from Chromobacterium violaceum is specific for tryptophan derivatives possessing its carboxyl group free or as an amide or ester, and an unsubstituted indole ring. Pyrroloquinoline-quinone synthase So far only a single turnover of the enzyme has been observed, and the pyrroloquinoline quinone remains bound to it; it is not yet known what releases the product in the bacterium. 6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,5,6,7,8-octahydroquinoline-2,4-dicarboxylate + 3 O(2) = 4,5-dioxo-3a,4,5,6,7,8,9,9b-octahydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H(2)O(2) + 2 H(2)O. L-galactonolactone oxidase L-xylono-1,4-lactone oxidase L-galactono-1,4-lactone + O(2) = L-ascorbate + H(2)O(2). Acts on the 1,4-lactones of L-galactonic, D-altronic, L-fuconic, D-arabinic and D-threonic acids. Not identical with EC 1.1.3.8 (cf. EC 1.3.2.3). FAD Coproporphyrinogenase Coproporphyrinogen oxidase Coprogen oxidase Coproporphyrinogen-III oxidase http://purl.uniprot.org/mim/121300 Coproporphyrinogen-III + O(2) + 2 H(+) = protoporphyrinogen-IX + 2 CO(2) + 2 H(2)O. Iron Protoporphyrinogen oxidase Protoporphyrinogenase Protoporphyrinogen-IX oxidase Also slowly oxidizes mesoporphyrinogen-IX. FAD Protoporphyrinogen-IX + 1.5 O(2) = protoporphyrin-IX + 3 H(2)O. http://purl.uniprot.org/mim/176200 Bilirubin oxidase 2 bilirubin + O(2) = 2 biliverdin + 2 H(2)O. Acyl-CoA oxidase Acyl-CoA + O(2) = trans-2,3-dehydroacyl-CoA + H(2)O(2). Acts on CoA derivatives of fatty acids with chain length from C(8) to C(18). http://purl.uniprot.org/mim/264470 FAD Dihydrouracil oxidase FMN 5,6-dihydrouracil + O(2) = uracil + H(2)O(2). Also oxidizes dihydrothymine to thymine. THB oxidase Tetrahydroberberine oxidase Flavoprotein (S)-tetrahydroberberine + 2 O(2) = berberine + 2 H(2)O(2). (R)-tetrahydroberberines are not oxidized. Secologanin synthase Loganin + NADPH + O(2) = secologanin + NADP(+) + 2 H(2)O. Heme-thiolate Secologanin is the precursor of the monoterpenoid indole alkaloids and ipecac alkaloids. With a quinone or related compound as acceptor Succinic dehydrogenase Succinate dehydrogenase (ubiquinone) FAD Iron-sulfur http://purl.uniprot.org/mim/256000 Succinate + ubiquinone = fumarate + ubiquinol. http://purl.uniprot.org/mim/171300 The complex, present in mitochondria, can be degraded to form EC 1.3.99.1, which no longer reacts with ubiquinone. http://purl.uniprot.org/mim/252011 http://purl.uniprot.org/mim/115310 With an iron-sulfur protein as acceptor 6-hydroxynicotinate reductase 6-oxotetrahydro-nicotinate dehydrogenase HNA reductase 6-hydroxynicotinic reductase Other enzymes involved in this pathway are EC 1.17.5.1, EC 3.5.2.18, EC 1.1.1.291, EC 5.4.99.4, EC 5.3.3.6, EC 4.2.1.85 and EC 4.1.3.32. Forms part of the nicotinate-fermentation catabolism pathway in Eubacterium barkeri. 6-oxo-1,4,5,6-tetrahydronicotinate + oxidized ferredoxin = 6-hydroxynicotinate + reduced ferredoxin. 15,16-dihydrobiliverdin:ferredoxin oxidoreductase Catalyzes the two-electron reduction of biliverdin IX-alpha at the C15 methine bridge. It has been proposed that this enzyme and EC 1.3.7.3 function as a dual enzyme complex in the conversion of biliverdin IX-alpha into phycoerythrobilin. 15,16-dihydrobiliverdin + oxidized ferredoxin = biliverdin IX-alpha + reduced ferredoxin. Phycoerythrobilin:ferredoxin oxidoreductase Catalyzes the two-electron reduction of the C2 and C3(1) diene system of 15,16-dihydrobiliverdin. It has been proposed that this enzyme and EC 1.3.7.2 function as a dual enzyme complex in the conversion of biliverdin IX-alpha into phycoerythrobilin. (3Z)-phycoerythrobilin + oxidized ferredoxin = 15,16-dihydrobiliverdin + reduced ferredoxin. Specific for 15,16-dihydrobiliverdin. Phytochromobilin:ferredoxin oxidoreductase Phytochromobilin synthase PFB synthase P-Phi-B synthase Can use 2Fe-2S ferredoxins from a number of sources as acceptor but not the 4Fe-4S ferredoxin from Clostridium pasteurianum. The isomerization of (3Z)-phytochromobilin to (3E)-phytochromobilin is thought to occur prior to covalent attachment to apophytochrome in the plant cell cytoplasm. Flavodoxins can be used instead of ferredoxin. Catalyzes the two-electron reduction of biliverdin IX-alpha. (3Z)-phytochromobilin + oxidized ferredoxin = biliverdin IX-alpha + reduced ferredoxin. Phycocyanobilin:ferredoxin oxidoreductase Catalyzes the four-electron reduction of biliverdin IX-alpha (2-electron reduction at both the A and D rings). Reaction proceeds via an isolatable 2-electron intermediate, 18(1),18(2)-dihydrobiliverdin. Flavodoxins can be used instead of ferredoxin. The direct conversion of biliverdin IX-alpha (BV) to (3Z)-phycocyanobilin (PCB) in the cyanobacteria Synechocystis sp. PCC 6803, Anabaena sp. PCC7120 and Nostoc punctiforme is in contrast to the proposed pathways of PCB biosynthesis in the red alga Cyanidium caldarium, which involves (3Z)-phycoerythrobilin (PEB) as an intermediate and in the green alga Mesotaenium caldariorum, in which PCB is an isolable intermediate. (3Z)-phycocyanobilin + oxidized ferredoxin = biliverdin IX-alpha + reduced ferredoxin. With other acceptors Fumarate reductase Fumarate dehydrogenase Fumaric hydrogenase Succinic dehydrogenase Succinate dehydrogenase FAD Succinate + acceptor = fumarate + reduced acceptor. Isovaleryl-CoA dehydrogenase 3-methylbutanoyl-CoA + acceptor = 3-methylbut-2-enoyl-CoA + reduced acceptor. Forms with another flavoprotein ('electron-transferring flavoprotein') and EC 1.5.5.1 a system reducing ubiquinone and other acceptors. FAD http://purl.uniprot.org/mim/243500 Not identical with EC 1.3.99.2, EC 1.3.99.3 or EC 1.3.99.12. n-pentanoate can act as donor. Dihydroorotate dehydrogenase Iron Zinc (S)-dihydroorotate + acceptor = orotate + reduced acceptor. Oxygen can act as acceptor, but much more slowly than 2,6-dichloroindophenol or 1,10-phenanthroline. 2-methylacyl-CoA dehydrogenase Branched-chain acyl-CoA dehydrogenase FAD Also oxidizes 2-methylpropanoyl-CoA. Not identical with EC 1.3.99.2, EC 1.3.99.3, EC 1.3.99.10 or EC 1.3.99.13. 2-methylbutanoyl-CoA + acceptor = 2-methylbut-2-enoyl-CoA + reduced acceptor. Long-chain-acyl-CoA dehydrogenase http://purl.uniprot.org/mim/201460 Acyl-CoA + acceptor = 2,3-dehydroacyl-CoA + reduced acceptor. FAD Forms with another flavoprotein ('electron-transferring flavoprotein') and EC 1.5.5.1 a system reducing ubiquinone and other acceptors. Not identical with EC 1.3.99.2, EC 1.3.99.3, EC 1.3.99.10 or EC 1.3.99.12. Cyclohexanone dehydrogenase 2,6-dichloroindophenol can act as acceptor. The corresponding ketones of cyclopentane and cycloheptane cannot act as donors. Cyclohexanone + acceptor = cyclohex-2-enone + reduced acceptor. Benzoyl-CoA reductase Benzoyl-CoA reductase (dearomatizing) Benzoyl-CoA + reduced acceptor + 2 ATP = cyclohexa-1,5-diene-1-carbonyl-CoA + acceptor + 2 ADP + 2 phosphate. Manganese or magnesium Reduced methyl viologen can act as electron donor. Inactive toward aromatic acids that are not CoA esters but will also catalyze the reaction: NH(3) + acceptor + 2 ADP + 2 phosphate + H(2)O = hydroxylamine + reduced acceptor + 2 ATP. In the presence of reduced acceptor, but in the absence of oxidizable substrate, the enzyme catalyzes the hydrolysis of ATP to ADP plus phosphate. Isoquinoline 1-oxidoreductase Electron acceptors include 1,2-benzoquinone, cytochrome c, ferricyanide, iodonitrotetrazolium chloride (INT), nitroblue tetrazolium (NBT), Meldola blue and phenazine methosulfate. The enzyme from Pseudomonas diminuta is specific toward N-containing N-heterocyclic substrates, including isoquinoline, isoquinolin-5-ol, phthalazine and quinazoline. Isoquinoline + acceptor + H(2)O = isoquinolin-1(2H)-one + reduced acceptor. Quinoline 2-oxidoreductase FAD In addition to quinoline, quinolin-2-ol, quinolin-7-ol, quinolin-8-ol, 3-, 4-and 8-methylquinolines and 8-chloroquinoline are substrates. Quinoline + acceptor + H(2)O = isoquinolin-1(2H)-one + reduced acceptor. Iron-sulfur Molybdenum Iodonitrotetrazolium chloride (INT) can act as an electron acceptor. Quinaldate 4-oxidoreductase Quinaldic acid 4-oxidoreductase Quinaldate + acceptor + H(2)O = kynurenate + reduced acceptor. 2,4,6-trinitrobenzene sulfonate acid, 1,4-benzoquinone, 1,2-naphthoquinone, nitroblue tetrazolium (NBT), thionine and menadione will serve as an electron acceptor for the former enzyme and ferricyanide for the latter; Meldola blue, iodonitrotetrazolium chloride (INT), phenazine methosulfate (PMS), 2,6-dichlorophenolindophenol (DCPIP) and cytochrome c will act as electron acceptors for both. The enzyme from Pseudomonas sp. AK2 also acts on quinoline-8-carboxylate, whereas that from Serratia marcescens 2CC-1 will oxidize nicotinate; quinaldate is a substrate for both of these enzymes. Quinoline-4-carboxylic acid 2-oxidoreductase Quinoline-4-carboxylate 2-oxidoreductase Quinaldic acid 4-oxidoreductase Quinoline-4-carboxylate + acceptor + H(2)O = 2-oxo-1,2-dihydroquinoline-4-carboxylate + reduced acceptor. Iodonitrotetrazolium chloride, thionine, menadione and 2,6-dichlorophenolindophenol can act as electron acceptors. Molybdopterin cytosine dinucleotide Iron-sulfur Quinoline, 4-methylquinoline and 4-chloroquinoline can also serve as substrates for the enzyme from Agrobacterium sp. 1B. Flavin Butyryl-CoA dehydrogenase Short-chain-acyl-CoA dehydrogenase Butyryl dehydrogenase Unsaturated acyl-CoA reductase Butanoyl-CoA + acceptor = 2-butenoyl-CoA + reduced acceptor. Forms with another flavoprotein ('electron-transferring flavoprotein') and EC 1.5.5.1 a system reducing ubiquinone and other acceptors. http://purl.uniprot.org/mim/201470 FAD 4-hydroxybenzoyl-CoA reductase 4-hydroxybenzoyl-CoA reductase (dehydroxylating) Flavin Involved in the anaerobic pathway of phenol metabolism in bacteria. Benzoyl-CoA + acceptor = 4-hydroxybenzoyl-CoA + reduced acceptor. A ferredoxin with two [4Fe-4S] clusters functions as the natural electron donor. Iron-sulfur Molybdenum (R)-benzylsuccinyl-CoA dehydrogenase Forms the third step in the anaerobic toluene metabolic pathway in Thauera aromatica. (R)-2-benzylsuccinyl-CoA + 2 electron-transferring flavoprotein = (E)-2-benzylidenesuccinyl-CoA + 2 reduced electron-transferring flavoprotein. Uses the ferricenium ion as the preferred artificial electron acceptor. FAD The enzyme is highly specific for (R)-benzylsuccinyl-CoA and is inhibited by (S)-benzylsuccinyl-CoA. Unlike other acyl-CoA dehydrogenases, this enzyme exhibits high substrate-and enantiomer specificity. Coproporphyrinogen III oxidase Coproporphyrinogen dehydrogenase Oxygen-independent coproporphyrinogen-III oxidase Radical SAM enzyme This conversion, -.CH-CH(2)-COO--> -CH=CH(2) + CO(2) + e(-) replaces the electron initially used. Occurs mainly in bacteria, whereas eukaryotes use the oxygen-dependent oxidase. Coproporphyrinogen-III + 2 S-adenosyl-L-methionine = protoporphyrinogen-IX + 2 CO(2) + 2 L-methionine + 2 5'-deoxyadenosine. Iron-sulfur The reaction starts by using an electron from the reduced form of the enzyme's [4Fe-4S] cluster to split AdoMet into methionine and the radical 5'-deoxyadenosin-5'-yl; this radical initiates attack on the 2-carboxyethyl groups, leading to their conversion into vinyl groups. Differs from EC 1.3.3.3 by using S-adenosyl-L-methionine (AdoMet) instead of oxygen as oxidant. Retinol saturase All-trans-13,14-dihydroretinol:acceptor 13,14-oxidoreductase RetSat All-trans-retinol 13,14-reductase (13,14)-all-trans-retinol saturase All-trans-13,14-dihydroretinol + acceptor = all-trans-retinol + reduced acceptor. May play a role in the metabolism of vitamin A. The reaction is only known to occur in the opposite direction to that given above, with the enzyme being specific for all-trans-retinol as substrate. Neither all-trans-retinoic acid nor 9-cis, 11-cis or 13-cis-retinol isomers are substrates. Acyl-CoA dehydrogenase Medium-chain acyl-CoA dehydrogenase Acyl dehydrogenase FAD http://purl.uniprot.org/mim/201450 Forms with another flavoprotein ('electron-transferring flavoprotein') and EC 1.5.5.1 a system reducing ubiquinone and other acceptors. Acyl-CoA + acceptor = 2,3-dehydroacyl-CoA + reduced acceptor. 3-oxosteroid 1-dehydrogenase A 3-oxosteroid + acceptor = a 3-oxo-Delta(1)-steroid + reduced acceptor. Steroid 5-alpha-reductase 3-oxo-5-alpha-steroid 4-dehydrogenase http://purl.uniprot.org/mim/264600 A 3-oxo-5-alpha-steroid + acceptor = a 3-oxo-Delta(4)-steroid + reduced acceptor. Delta(4)-3-ketosteroid 5-beta-reductase 3-oxo-5-beta-steroid 4-dehydrogenase A 3-oxo-5-beta-steroid + acceptor = a 3-oxo-Delta(4)-steroid + reduced acceptor. Glutaryl-CoA dehydrogenase FAD http://purl.uniprot.org/mim/231670 Glutaryl-CoA + acceptor = crotonoyl-CoA + CO(2) + reduced acceptor. 2-furoyl-CoA dehydrogenase Furoyl-CoA hydroxylase 2-furoyl-CoA + H(2)O + acceptor = S-(5-hydroxy-2-furoyl)-CoA + reduced acceptor. Copper Methylene blue, nitro blue tetrazolium and a membrane fraction from Pseudomonas putida can act as acceptors. The actual oxidative step is probably dehydrogenation of a hydrated form -CHOH-CH(2)-to -C(OH)=CH-, which tautomerizes non-enzymically to -CO-CH(2)-, giving (5-oxo-4,5-dihydro-2-furoyl)-CoA. The oxygen atom of the -OH produced is derived from water, not O(2). Acting on the CH-NH(2) group of donors With NAD(+) or NADP(+) as acceptor Alanine dehydrogenase L-alanine + H(2)O + NAD(+) = pyruvate + NH(3) + NADH. Glycine dehydrogenase Glycine + H(2)O + NAD(+) = glyoxylate + NH(3) + NADH. L-erythro-3,5-diaminohexanoate dehydrogenase L-erythro-3,5-diaminohexanoate + H(2)O + NAD(+) = (S)-5-amino-3-oxohexanoate + NH(3) + NADH. 2,4-diaminopentanoate dehydrogenase Also acts, more slowly, on 2,5-diaminohexanoate forming 2-amino-5-oxohexanoate, which then cyclizes non-enzymically to 1-pyrroline-2-methyl-5-carboxylate. 2,4-diaminopentanoate + H(2)O + NAD(P)(+) = 2-amino-4-oxopentanoate + NH(3) + NAD(P)H. Glutamine amide-2-oxoglutarate aminotransferase (oxidoreductase, NADP) Glutamate synthetase (NADP) Glutamate synthase (NADPH) L-glutamine:2-oxoglutarate aminotransferase, NADPH oxidizing Glutamine-ketoglutaric aminotransferase NADPH-glutamate synthase NADPH-dependent glutamate synthase GOGAT L-glutamate synthase Glutamate (reduced nicotinamide adenine dinucleotide phosphate) synthase L-glutamate synthetase FMN 2 L-glutamate + NADP(+) = L-glutamine + 2-oxoglutarate + NADPH. Iron-sulfur FAD NADH-dependent glutamate synthase NADH-glutamate synthase L-glutamate synthase Glutamate synthase (NADH) L-glutamate synthetase FMN 2 L-glutamate + NAD(+) = L-glutamine + 2-oxoglutarate + NADH. Lysine dehydrogenase L-lysine + NAD(+) = 1,2-didehydropiperidine-2-carboxylate + NH(3) + NADH. Meso-diaminopimelate D-dehydrogenase Diaminopimelate dehydrogenase Meso-2,6-diaminoheptanedioate + H(2)O + NADP(+) = L-2-amino-6-oxoheptanedioate + NH(3) + NADPH. N-methylalanine dehydrogenase N-methyl-L-alanine + H(2)O + NADP(+) = pyruvate + methylamine + NADPH. Lysine 6-dehydrogenase LysDH L-lysine epsilon-dehydrogenase L-lysine 6-dehydrogenase L-lysine + NAD(+) = (S)-2,3,4,5-tetrahydropiperidine-2-carboxylate + NADH + NH(3). While the enzyme from Agrobacterium tumefaciens can use only NAD(+), that from the thermophilic bacterium Geobacillus stearothermophilus can also use NADP(+), but more slowly. Highly specific for L-lysine as substrate, although (S)-(beta-aminoethyl)-L-cysteine can act as a substrate, but more slowly. TrpDH L-Trp-dehydrogenase L-tryptophan dehydrogenase Tryptophan dehydrogenase Calcium L-tryptophan + NAD(P)(+) = (indol-3-yl)pyruvate + NH(3) + NAD(P)H. Glutamic dehydrogenase Glutamate dehydrogenase L-glutamate + H(2)O + NAD(+) = 2-oxoglutarate + NH(3) + NADH. Phenylalanine dehydrogenase L-phenylalanine dehydrogenase PheDH L-phenylalanine + H(2)O + NAD(+) = phenylpyruvate + NH(3) + NADH. The enzymes from Bacillus badius and Sporosarcina ureae are highly specific for L-phenylalanine; that from Bacillus sphaericus also acts on L-tyrosine. Aspartate dehydrogenase NAD-dependent aspartate dehydrogenase NADH(2)-dependent aspartate dehydrogenase NADP(+)-dependent aspartate dehydrogenase Catalyzes the first step in NAD biosynthesis from aspartate. Strictly specific for L-aspartate as substrate. Has a higher affinity for NAD(+) than NADP(+). L-aspartate + H(2)O + NAD(P)(+) = oxaloacetate + NH(3) + NAD(P)H. Glutamic dehydrogenase Glutamate dehydrogenase (NAD(P)(+)) L-glutamate + H(2)O + NAD(P)(+) = 2-oxoglutarate + NH(3) + NAD(P)H. http://purl.uniprot.org/mim/606762 Glutamate dehydrogenase (NADP(+)) Glutamic dehydrogenase L-glutamate + H(2)O + NADP(+) = 2-oxoglutarate + NH(3) + NADPH. L-amino-acid dehydrogenase Acts on aliphatic amino acids. An L-amino acid + H(2)O + NAD(+) = a 2-oxo acid + NH(3) + NADH. L-serine:NAD oxidoreductase (deaminating) Serine dehydrogenase Serine 2-dehydrogenase L-serine + H(2)O + NAD(+) = 3-hydroxypyruvate + NH(3) + NADH. Valine dehydrogenase (NADP(+)) L-valine + H(2)O + NADP(+) = 3-methyl-2-oxobutanoate + NH(3) + NADPH. Leucine dehydrogenase LeuDH Also acts on isoleucine, valine, norvaline and norleucine. L-leucine + H(2)O + NAD(+) = 4-methyl-2-oxopentanoate + NH(3) + NADH. With a cytochrome as acceptor Glycine-cytochrome c reductase Glycine dehydrogenase (cytochrome) Glycine + H(2)O + 2 ferricytochrome c = glyoxylate + NH(3) + 2 ferrocytochrome c + 2 H(+). With oxygen as acceptor Aspartic oxidase D-aspartate oxidase FAD D-aspartate + H(2)O + O(2) = oxaloacetate + NH(3) + H(2)O(2). Putrescine oxidase 4-aminobutanal condenses non-enzymically to 1-pyrroline. FAD Putrescine + O(2) + H(2)O = 4-aminobutanal + NH(3) + H(2)O(2). L-glutamate oxidase FAD The enzyme from Azotobacter previously listed under this number, which did not produce H(2)O(2), was a crude cell-free extract which probably contained catalase. L-glutamate + O(2) + H(2)O = 2-oxoglutarate + NH(3) + H(2)O(2). Cyclohexylamine oxidase Cyclohexylamine + O(2) + H(2)O = cyclohexanone + NH(3) + H(2)O(2). Some other cyclic amines can act instead of cyclohexylamine, but not simple aliphatic and aromatic amides. FAD Lysyl oxidase Protein-lysine 6-oxidase Also acts on protein 5-hydroxylysine. These reactions play an important role for the development, elasticity and extensibility of connective tissue. Peptidyl-L-lysyl-peptide + O(2) + H(2)O = peptidyl-allysyl-peptide + NH(3) + H(2)O(2). Catalyzes the final known enzymic step required for collagen and elastin cross-linking in the biosynthesis of normal mature extracellular matrices. Also active on free amines, such as cadaverine or benzylamine. L-lysine oxidase L-lysine + O(2) + H(2)O = 6-amino-2-oxohexanoate + NH(3) + H(2)O(2). FAD Also acts, more slowly, on L-ornithine, L-phenylalanine, L-arginine and L-histidine. D-glutamate(D-aspartate) oxidase D-glutamate and D-aspartate are oxidized at the same rate. FAD Other D-monoaminodicarboxylates, and other D-and L-amino acids, are not oxidized. D-glutamate + H(2)O + O(2) = 2-oxoglutarate + NH(3) + H(2)O(2). L-aspartate oxidase A component of the bacterial quinolinate synthase system. L-aspartate + H(2)O + O(2) = oxaloacetate + NH(3) + H(2)O(2). FAD Glycine oxidase (1) Glycine + H(2)O + O(2) = glyoxylate + NH(3) + H(2)O(2). FAD (3) Sarcosine + H(2)O + O(2) = glyoxylate + methylamine + H(2)O(2). The enzyme from Bacillus subtilis is active with glycine, sarcosine, N-ethylglycine, D-alanine, D-alpha-aminobutyrate, D-proline, D-pipecolate and N-methyl-D-alanine. (2) D-alanine + H(2)O + O(2) = pyruvate + NH(3) + H(2)O(2). It differs from EC 1.4.3.3 due to its activity on sarcosine and D-pipecolate. (4) N-ethylglycine + H(2)O + O(2) = glyoxylate + ethylamine + H(2)O(2). L-amino-acid oxidase Ophio-amino-acid oxidase An L-amino acid + H(2)O + O(2) = a 2-oxo acid + NH(3) + H(2)O(2). FAD Marinocine L-lysine-epsilon-oxidase Lod L-lysine 6-oxidase The amines cadaverine and putrescine are not substrates. L-lysine + O(2) + H(2)O = 2-aminoadipate 6-semialdehyde + H(2)O(2) + NH(3). Differs from EC 1.4.3.13 by using free L-lysine rather than the protein-bound form. Also acts on L-ornithine, D-lysine and 4-hydroxy-L-lysine, but more slowly. N(2)-acetyl-L-lysine is also a substrate, but N(6)-acetyl-L-lysine, which has an acetyl group at position 6, is not. D-amino-acid oxidase FAD Wide specificity for D-amino acids. Also acts on glycine. A D-amino acid + H(2)O + O(2) = a 2-oxo acid + NH(3) + H(2)O(2). Tyraminase Amine oxidase Tyramine oxidase Amine oxidase (flavin-containing) Monoamine oxidase Adrenaline oxidase RCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2). FAD Acts on primary amines, and usually also on secondary and tertiary amines. http://purl.uniprot.org/mim/300615 Pyridoxal 5'-phosphate synthase Pyridoxamine 5'-phosphate oxidase PMP oxidase Pyridoxamine phosphate oxidase Pyridoxamine-phosphate oxidase Pyridoxine (pyridoxamine) 5'-phosphate oxidase Pyridoxine (pyridoxamine)phosphate oxidase In Escherichia coli, the coenzyme pyridoxal 5'-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72, EC 1.1.1.290, EC 2.6.1.52, EC 1.1.1.262, EC 2.6.99.2 and EC 1.4.3.5. FMN (1) Pyridoxamine 5'-phosphate + H(2)O + O(2) = pyridoxal 5'-phosphate + NH(3) + H(2)O(2). http://purl.uniprot.org/mim/610090 (2) Pyridoxine 5'-phosphate + O(2) = pyridoxal 5'-phosphate + H(2)O(2). DAO Histaminase Diamine oxidase Diamino oxhydrase Amine oxidase (copper-containing) Copper A group of enzymes including those oxidizing primary amines, diamines and histamine. Topaquinone One form of EC 1.3.1.15 from rat kidney also catalyzes this reaction. RCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2). D-glutamate oxidase D-glutamic oxidase D-glutamate + H(2)O + O(2) = 2-oxoglutarate + NH(3) + H(2)O(2). Ethanolamine oxidase Cobalt Ethanolamine + H(2)O + O(2) = glycolaldehyde + NH(3) + H(2)O(2). With a disulfide as acceptor Glycine decarboxylase Glycine cleavage system P-protein Glycine-cleavage complex P-protein Glycine dehydrogenase (decarboxylating) The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein. Pyridoxal-phosphate A component, with EC 2.1.2.10 and EC 1.8.1.4, of the glycine cleavage system, previously known as glycine synthase. http://purl.uniprot.org/mim/605899 Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2). With an iron-sulfur protein as acceptor Glutamate synthase (ferredoxin) Ferredoxin-dependent glutamate synthase Flavoprotein 2 L-glutamate + 2 oxidized ferredoxin = L-glutamine + 2-oxoglutarate + 2 reduced ferredoxin + 2 H(+). Iron-sulfur With other acceptors D-amino-acid dehydrogenase FAD A D-amino acid + H(2)O + acceptor = a 2-oxo acid + NH(3) + reduced acceptor. Acts to some extent on all D-amino acids except D-aspartate and D-glutamate. Taurine dehydrogenase Taurine + H(2)O + acceptor = sulfoacetaldehyde + NH(3) + reduced acceptor. Primary-amine dehydrogenase MADH Methylamine dehydrogenase Amine dehydrogenase RCH(2)NH(2) + H(2)O + acceptor = RCHO + NH(3) + reduced acceptor. Tryptophan tryptophylquinone (TTQ) Aromatic amine dehydrogenase Aralkylamine dehydrogenase Acts on aromatic amines and, more slowly, on some long-chain aliphatic amines, but not on methylamine or ethylamine (cf. EC 1.4.99.3). Phenazine methosulfate can act as acceptor. RCH(2)NH(2) + H(2)O + acceptor = RCHO + NH(3) + reduced acceptor. Glycine dehydrogenase (cyanide-forming) Hydrogen cyanide synthase HCN synthase The enzyme is membrane-bound, and the 2-electron acceptor is a component of the respiratory chain. The enzyme can act with various artificial electron acceptors, including phenazine methosulfate. Glycine + 2 A = HCN + CO(2) + 2 AH(2). FAD Acting on the CH-NH group of donors With NAD(+) or NADP(+) as acceptor Pyrroline-2-carboxylate reductase Reduces 1-pyrroline-2-carboxylate to L-proline and also 1,2-didehydropiperidine-2-carboxylate to L-pipecolate. L-proline + NAD(P)(+) = 1-pyrroline-2-carboxylate + NAD(P)H. Aminoadipic semialdehyde-glutamic reductase Aminoadipic semialdehyde-glutamate reductase Aminoadipate semialdehyde-glutamate reductase Saccharopine reductase Saccharopine dehydrogenase (NADP(+), L-glutamate-forming) N(6)-(L-1,3-dicarboxypropyl)-L-lysine + NADP(+) + H(2)O = L-glutamate + L-2-aminoadipate 6-semialdehyde + NADPH. D-octopine synthase Octopine dehydrogenase ODH D-octopine dehydrogenase N(2)-(D-1-carboxyethyl)-L-arginine + NAD(+) + H(2)O = L-arginine + pyruvate + NADH. Also acts, in the reverse direction, on L-ornithine, L-lysine and L-histidine. 1-pyrroline-5-carboxylate dehydrogenase Oxidizes other 1-pyrrolines, e.g. 3-hydroxy-1-pyrroline-5-carboxylate forms 4-hydroxyglutamate. http://purl.uniprot.org/mim/239510 1-pyrroline-5-carboxylate + NAD(+) + H(2)O = L-glutamate + NADH. Methylenetetrahydrofolate dehydrogenase (NAD(+)) 5,10-methylenetetrahydrofolate + NAD(+) = 5,10-methenyltetrahydrofolate + NADH. D-lysopine dehydrogenase Lysopine dehydrogenase D-lysopine synthase In the reverse reaction, a number of L-amino acids can act instead of L-lysine, and 2-oxobutanoate and, to a lesser extent, glyoxylate can act instead of pyruvate. N(2)-(D-1-carboxyethyl)-L-lysine + NADP(+) + H(2)O = L-lysine + pyruvate + NADPH. Alanopine dehydrogenase 2,2'-iminodipropanoate + NAD(+) + H(2)O = L-alanine + pyruvate + NADH. In the reverse reaction, L-alanine can be replaced by L-cysteine, L-serine, or L-threonine; glycine acts very slowly (cf. EC 1.5.1.22). Ephedrine dehydrogenase Acts on a number of related compounds including (-)-sympatol, (+)-pseudoephedrine and (+)-norephedrine. The product immediately hydrolyzes to methylamine and 1-hydroxy-1-phenylpropan-2-one. (-)-ephedrine + NAD(+) = (R)-2-methylimino-1-phenylpropan-1-ol + NADH. Nopaline dehydrogenase D-nopaline dehydrogenase D-nopaline synthase NOS Nopaline synthase N(2)-(D-1,3-dicarboxypropyl)-L-arginine + NADP(+) + H(2)O = L-arginine + 2-oxoglutarate + NADPH. In the reverse direction, forms D-nopaline from L-arginine and D-ornaline from L-ornithine. P5CR Pyrroline-5-carboxylate reductase L-proline + NAD(P)(+) = 1-pyrroline-5-carboxylate + NAD(P)H. Also reduces 1-pyrroline-3-hydroxy-5-carboxylate to L-hydroxyproline. 5,10-methylenetetrahydropteroylglutamate reductase 5-methyltetrahydrofolate:(acceptor) oxidoreductase Methylenetetrahydrofolic acid reductase 5-methyltetrahydrofolate:NAD(+) oxidoreductase Methylenetetrahydrofolate reductase (NADPH(2)) Methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase 5-methyltetrahydrofolate:NAD oxidoreductase 5,10-methylenetetrahydrofolate reductase 5,10-methylenetetrahydrofolic acid reductase Methylenetetrahydrofolate reductase (NADPH) 5,10-methylenetetrahydrofolate reductase (NADPH) Methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate) reductase N(5,10)-methylenetetrahydrofolate reductase N(5),N(10)-methylenetetrahydrofolate reductase MTHFR 5,10-CH(2)-H(4)folate reductase 5-methyltetrahydrofolate:NADP(+) oxidoreductase 5,10-methylenetetrahydrofolate reductase (FADH(2)) Methylenetetrahydrofolate reductase Methylenetetrahydrofolate reductase (NAD(P)H) http://purl.uniprot.org/mim/236250 5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H. Menadione can also serve as an electron acceptor. FAD Delta(1)-piperideine-2-carboxylate reductase L-pipecolate + NADP(+) = Delta(1)-piperideine-2-carboxylate + NADPH. Strombine dehydrogenase N-(carboxymethyl)-D-alanine + NAD(+) + H(2)O = glycine + pyruvate + NADH. Catalyzes the reaction of EC 1.5.1.17, more slowly. Does not act on L-strombine. Tauropine dehydrogenase In the reverse reaction, alanine can act instead of taurine, more slowly, and 2-oxobutanoate and 2-oxopentanoate can act instead of pyruvate. Tauropine + NAD(+) + H(2)O = taurine + pyruvate + NADH. N(5)-(carboxyethyl)ornithine synthase N(5)-(L-1-carboxyethyl)-L-ornithine + NADP(+) + H(2)O = L-ornithine + pyruvate + NADPH. In the reverse direction L-lysine can act instead of L-ornithine, more slowly. Acts on the amino group (cf. EC 1.5.1.16). Ketimine reductase Thiomorpholine-carboxylate dehydrogenase In the reverse direction, a number of other cyclic unsaturated compounds can act as substrates, more slowly. The product is the cyclic imine of the 2-oxoacid corresponding to S-(2-aminoethyl)cysteine. Thiomorpholine 3-carboxylate + NAD(P)(+) = 3,4-dehydro-thiomorpholine-3-carboxylate + NAD(P)H. Beta-alanopine dehydrogenase Beta-alanopine + NAD(+) + H(2)O = beta-alanine + pyruvate + NADH. 1,2-dehydroreticulinium reductase (NADPH) 1,2-dehydroreticulinium ion reductase (R)-reticuline + NADP(+) = 1,2-dehydroreticulinium + NADPH. The enzyme does not catalyze the reverse reaction to any significant extent under physiological conditions. Reduces the 1,2-dehydroreticulinium ion to (R)-reticuline, which is a direct precursor of morphinan alkaloids in the poppy plant. Opine dehydrogenase In the reverse direction, the enzyme acts also on neutral amino acids as an amino donor. Dehydrogenation forms an imine, which dissociates to the amino acid and pyruvate. In the forward direction, the enzyme from Arthrobacter sp. acts also on secondary amine dicarboxylates such as N-(1-carboxyethyl)methionine and N-(1-carboxyethyl)phenylalanine. The amino acceptors include 2-oxoacids such as pyruvate, oxaloacetate, glyoxylate and 2-oxobutyrate. They include L-amino acids such as 2-aminopentanoic acid, 2-aminobutyric acid, 2-aminohexanoic acid, 3-chloroalanine, O-acetylserine, methionine, isoleucine, valine, phenylalanine, leucine and alanine. (2S)-2-((1-(R)-carboxyethyl)amino)pentanoate + NAD(+) + H(2)O = L-2-aminopentanoic acid + pyruvate + NADH. FMN reductase NAD(P)H:FMN oxidoreductase Flavine mononucleotide reductase NAD(P)H-dependent FMN reductase NAD(P)H:flavin oxidoreductase NAD(P)H(2) dehydrogenase (FMN) NAD(P)H-FMN reductase Riboflavin mononucleotide (reduced nicotinamide adenine dinucleotide (phosphate)) reductase Riboflavin mononucleotide reductase NAD(P)H dehydrogenase (FMN) Flavin mononucleotide reductase Riboflavine mononucleotide reductase NAD(P)H(2):FMN oxidoreductase The enzyme from luminescent bacteria and the SsuE enzyme from Escherichia coli also reduce riboflavin and FAD, but more slowly. FMNH(2) + NAD(P)(+) = FMN + NAD(P)H. In E.coli, this enzyme, in conjunction with EC 1.14.14.5, forms a two-component alkanesulfonate monooxygenase, which allows for utilization of alkanesulfonates as sulfur sources under conditions of sulfate and cysteine starvation. Dihydrofolate reductase Tetrahydrofolate dehydrogenase The enzyme from animals and some micro-organisms also slowly reduces folate to 5,6,7,8-tetrahydrofolate. http://purl.uniprot.org/mim/126060 5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH. NADPH-flavin reductase NADPH dehydrogenase (flavin) Riboflavin mononucleotide (reduced nicotinamide adenine dinucleotide phosphate) reductase NADPH-dependent FMN reductase NADPH-FMN reductase Flavine mononucleotide reductase NADPH:flavin oxidoreductase NADPH:riboflavin oxidoreductase Riboflavin mononucleotide reductase Flavin mononucleotide reductase Riboflavine mononucleotide reductase NADPH-specific FMN reductase FMN reductase (NADPH) Flavin reductase Reduced riboflavin + NADP(+) = riboflavin + NADPH. NADH is oxidized more slowly than NADPH. The enzyme from Entamoeba histolytica reduces riboflavin and galactoflavin, and, more slowly, FMN and FAD. Berberine reductase (R)-canadine synthase (R)-canadine + 2 NADP(+) = berberine + 2 NADPH. Also acts on 7,8-dihydroberberine. Involved in alkaloid biosynthesis in Corydalis cava to give (R)-canadine with the opposite configuration to the precursor of berberine (see EC 1.3.3.8). Vomilenine reductase 1,2-dihydrovomilenine + NADP(+) = vomilenine + NADPH. Forms part of the ajmaline biosynthesis pathway. Pteridine reductase Pteridine reductase 1 PTR1 5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = biopterin + 2 NADPH. The enzyme is specific for NADPH; no activity has been detected with NADH. It also catalyzes the reduction of 7,8-dihydropterins and 7,8-dihydrofolate to their tetrahydro forms. It also differs from EC 1.5.1.3 in being specific for the B side of NADPH. In contrast to EC 1.5.1.3 and EC 1.5.1.34, pteridine reductase will not catalyze the reduction of the quinonoid form of dihydrobiopterin. The enzyme from Leishmania (both amastigote and promastigote forms) catalyzes the NADPH-dependent reduction of folate and a wide variety of unconjugated pterins, including biopterin, to their tetrahydro forms. NADPH-dihydropteridine reductase NAD(P)H(2):6,7-dihydropteridine oxidoreductase 6,7-dihydropteridine reductase Dihydropteridine reductase (NADH) Dihydropteridine reductase 6,7-dihydropteridine:NAD(P)H oxidoreductase Dihydropteridine (reduced nicotinamide adenine dinucleotide) reductase DHPR NADH-dihydropteridine reductase NADPH-specific dihydropteridine reductase Not identical with EC 1.5.1.3. The substrate is the quinonoid form of dihydropteridine. A 5,6,7,8-tetrahydropteridine + NAD(P)(+) = a 6,7-dihydropteridine + NAD(P)H. http://purl.uniprot.org/mim/261630 Transferred to EC 1.2.1.19 Methylenetetrahydrofolate dehydrogenase (NADP(+)) http://purl.uniprot.org/mim/172460 5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH. Formyltetrahydrofolate dehydrogenase 10-formyltetrahydrofolate dehydrogenase 10-formyltetrahydrofolate + NADP(+) + H(2)O = tetrahydrofolate + CO(2) + NADPH. Lysine-2-oxoglutarate reductase Saccharopine dehydrogenase (NAD(+), L-lysine-forming) N(6)-(L-1,3-dicarboxypropyl)-L-lysine + NAD(+) + H(2)O = L-lysine + 2-oxoglutarate + NADH. Lysine-ketoglutarate reductase Lysine-2-oxoglutarate reductase Saccharopine dehydrogenase (NADP(+), L-lysine-forming) http://purl.uniprot.org/mim/268700 N(6)-(L-1,3-dicarboxypropyl)-L-lysine + NADP(+) + H(2)O = L-lysine + 2-oxoglutarate + NADPH. Saccharopin dehydrogenase Saccharopine dehydrogenase (NAD(+), L-glutamate-forming) Aminoadipic semialdehyde synthase N(6)-(L-1,3-dicarboxypropyl)-L-lysine + NAD(+) + H(2)O = L-glutamate + 2-aminoadipate 6-semialdehyde + NADH. http://purl.uniprot.org/mim/238700 With oxygen as acceptor Sarcosine oxidase The flavin is both covalently and non-covalently bound in a molar ratio of 1:1. Sarcosine + H(2)O + O(2) = glycine + formaldehyde + H(2)O(2). FAD Dimethylglycine oxidase Does not oxidize sarcosine. FAD N,N-dimethylglycine + H(2)O + O(2) = sarcosine + formaldehyde + H(2)O(2). Polyamine oxidase Also acts on N(1)-acetylspermidine and N(1),N(12)-diacetylspermine. FAD N(1)-acetylspermine + O(2) + H(2)O = N(1)-acetylspermidine + 3-aminopropanal + H(2)O(2). Iron Dihydrobenzophenanthridine oxidase Found in higher plants. Produces oxidized forms of the benzophenanthridine alkaloids. (1) Dihydrosanguinarine + O(2) = sanguinarine + H(2)O(2). (3) Dihydromacarpine + O(2) = macarpine + H(2)O(2). Copper (2) Dihydrochelirubine + O(2) = chelirubine + H(2)O(2). N-methyl-L-amino-acid oxidase Flavoprotein An N-methyl-L-amino acid + H(2)O + O(2) = an L-amino acid + formaldehyde + H(2)O(2). Epsilon-alkyllysinase N(6)-methyllysine oxidase N(6)-methyl-lysine oxidase Epsilon-N-methyllysine demethylase N(6)-methyl-L-lysine + H(2)O + O(2) = L-lysine + formaldehyde + H(2)O(2). (S)-6-hydroxynicotine oxidase (S)-6-hydroxynicotine + H(2)O + O(2) = 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one + H(2)O(2). FAD (R)-6-hydroxynicotine oxidase FAD (R)-6-hydroxynicotine + H(2)O + O(2) = 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one + H(2)O(2). L-pipecolate oxidase The product reacts with water to form 2-aminoadipate 6-semialdehyde, i.e. 2-amino-6-oxohexanoate. L-pipecolate + O(2) = 2,3,4,5-tetrahydropyridine-2-carboxylate + H(2)O(2). With a disulfide as acceptor Pyrimidodiazepine synthase Involved in the formation of the eye pigment drosopterin in Drosophila melanogaster. A pyrimidodiazepine + glutathione disulfide + H(2)O = 6-pyruvoyl-tetrahydropterin + 2 glutathione. In the reverse direction of reaction, the reduction of 6-pyruvoyl-tetrahydropterin is accompanied by the opening of the 6-membered pyrazine ring and the formation of the 7-membered diazepine ring. The pyrimidodiazepine involved is an acetyldihydro derivative. With a quinone or similar compound as acceptor Electron-transferring-flavoprotein dehydrogenase ETF-QO ETF-ubiquinone oxidoreductase Electron transfer flavoprotein-ubiquinone oxidoreductase ETF dehydrogenase Iron-sulfur Forms part of the mitochondrial electron-transfer system. http://purl.uniprot.org/mim/231680 Reduced electron-transferring flavoprotein + ubiquinone = electron-transferring flavoprotein + ubiquinol. FAD With an iron-sulfur protein as acceptor 5,10-methylenetetrahydrofolate reductase Methylenetetrahydrofolate reductase (ferredoxin) The enzyme from Clostridium formicoaceticum catalyzes the reduction of methylene blue, menadione, benzyl viologen, rubredoxin or FAD with 5-methyltetrahydrofolate and the oxidation of reduced ferredoxin or FADH(2) with 5,10-methylenetetrahydrofolate. Flavoprotein 5-methyltetrahydrofolate + 2 oxidized ferredoxin = 5,10-methylenetetrahydrofolate + 2 reduced ferredoxin + 2 H(+). However, unlike EC 1.5.1.20, there is no activity with NAD(P)H. Iron-sulfur Zinc With a flavin as acceptor Dimethylamine dehydrogenase DMADh Dimethylamine + H(2)O + electron-transferring flavoprotein = methylamine + formaldehyde + reduced electron-transferring flavoprotein. FAD Iron-sulfur Trimethylamine dehydrogenase TMADh Phenazine methosulfate and 2,6-dichloroindophenol can act as electron acceptors. FMN Iron-sulfur A number of alkyl-substituted derivatives of trimethylamine can also act as electron donors. Trimethylamine + H(2)O + electron-transferring flavoprotein = dimethylamine + formaldehyde + reduced electron-transferring flavoprotein. With other acceptors Sarcosine dehydrogenase http://purl.uniprot.org/mim/268900 Sarcosine + acceptor + H(2)O = glycine + formaldehyde + reduced acceptor. FMN 5,10-methylenetetrahydromethanopterin reductase N(5),N(10)-methylenetetrahydromethanopterin:coenzyme-F420 oxidoreductase 5,10-methylenetetrahydromethanopterin cyclohydrolase Coenzyme F420-dependent N(5),N(10)-methenyltetrahydromethanopterin reductase Methylene-H(4)MPT reductase N(5),N(10)-methylenetetrahydromethanopterin reductase 5-methyltetrahydromethanopterin + coenzyme F420 = 5,10-methylenetetrahydromethanopterin + reduced coenzyme F420. Catalyzes an intermediate step in methanogenesis from CO(2) and H(2) in archaea. Cytokinin dehydrogenase Cytokinin oxidase N(6)-dimethylallyladenine + acceptor + H(2)O = adenine + 3-methylbut-2-enal + reduced acceptor. FAD Although this activity was previously thought to be catalyzed by a hydrogen-peroxide-forming oxidase, this enzyme does not require oxygen for activity and does not form hydrogen peroxide. Converts zeatin and related cytokinins. Catalyzes the oxidation of cytokinins, a family of N(6)-substituted adenine derivatives that are plant hormones, where the substituent is a dimethylallyl or other prenyl group. 2,6-dichloroindophenol, methylene blue, nitroblue tetrazolium, phenazine methosulfate and Cu(2+) in the presence of imidazole can act as acceptors. Dimethylglycine dehydrogenase N,N-dimethylglycine + acceptor + H(2)O = sarcosine + formaldehyde + reduced acceptor. FAD http://purl.uniprot.org/mim/605850 L-pipecolate dehydrogenase The product reacts with water to form 2-aminoadipate 6-semialdehyde, i.e. 2-amino-6-oxohexanoate. L-pipecolate + acceptor = 2,3,4,5-tetrahydropyridine-2-carboxylate + reduced acceptor. Nicotine dehydrogenase Nicotine + acceptor + H(2)O = (S)-6-hydroxynicotine + reduced acceptor. Acts on both (R)-and (S)-isomers. FMN Methylglutamate dehydrogenase N-methyl-L-glutamate + acceptor + H(2)O = L-glutamate + formaldehyde + reduced acceptor. A number of N-methyl-substituted amino acids can act as donors. 2,6-dichloroindophenol is the best acceptor. Spermidine dehydrogenase 4-aminobutanal condenses non-enzymically to 1-pyrroline. FAD Heme Ferricyanide, 2,6-dichloroindophenol and cytochrome c can act as acceptor. Spermidine + acceptor + H(2)O = 1,3-diaminopropane + 4-aminobutanal + reduced acceptor. Proline dehydrogenase L-proline + acceptor + H(2)O = (S)-1-pyrroline-5-carboxylate + reduced acceptor. http://purl.uniprot.org/mim/181500 FAD http://purl.uniprot.org/mim/239500 5,10-methylenetetrahydromethanopterin dehydrogenase N(5),N(10)-methylenetetrahydromethanopterin dehydrogenase Methylenetetrahydromethanopterin dehydrogenase Coenzyme F420 is a 7,8-didemethyl-8-hydroxy-5-deazariboflavin derivative; methanopterin is a pterin analog. The enzyme is involved in the formation of methane from CO(2) in Methanobacterium thermoautotrophicum. 5,10-methylenetetrahydromethanopterin + coenzyme F420 = 5,10-methenyltetrahydromethanopterin + reduced coenzyme F420. Acting on NADH or NADPH With NAD(+) or NADP(+) as acceptor Nicotinamide nucleotide transhydrogenase NAD(P)(+) transhydrogenase (B-specific) Pyridine nucleotide transhydrogenase NADPH + NAD(+) = NADP(+) + NADH. FAD B-specific with respect to both NAD(+) and NADP(+). Also acts with deamino coenzymes. NAD(P)(+) transhydrogenase (AB-specific) Pyridine nucleotide transhydrogenase Transhydrogenase The enzyme from heart mitochondria is A-specific with respect to NAD(+) and B-specific with respect to NADP(+) (cf. EC 1.6.1.1.). NADPH + NAD(+) = NADP(+) + NADH. With a heme protein as acceptor Cytochrome-b5 reductase FAD NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5. http://purl.uniprot.org/mim/250800 CPR TPNH(2) cytochrome c reductase NADPH:P450 reductase Aldehyde reductase (NADPH-dependent) Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase NADPH--cytochrome P450 oxidoreductase NADPH:ferrihemoprotein oxidoreductase NADPH--hemoprotein reductase TPNH-cytochrome c reductase NADPH--cytochrome c reductase NADPH--cytochrome c oxidoreductase Ferrihemoprotein P-450 reductase NADPH--cytochrome P450 reductase NADP--cytochrome c reductase NADPH--ferrihemoprotein reductase Reductase, cytochrome c (reduced nicotinamide adenine dinucleotide phosphate) NADPH--ferricytochrome c oxidoreductase Dihydroxynicotinamide adenine dinucleotide phosphate-cytochrome c reductase NADP--cytochrome reductase NADPH-dependent cytochrome c reductase Cytochrome P450 reductase FAD-cytochrome c reductase Cytochrome c reductase (reduced nicotinamide adenine dinucleotide phosphate, NADPH, NADPH-dependent) The enzyme catalyzes the reduction of the heme-thiolate-dependent monooxygenases, such as EC 1.14.14.1, and reduction of EC 1.14.99.3. The number n in the equation is 1 if the hemoprotein undergoes a 2-electron reduction, and is 2 if it undergoes a 1-electron reduction. FMN NADPH + n oxidized hemoprotein = NADP(+) + n reduced hemoprotein. It also reduces cytochrome b5 and cytochrome c. It is part of the microsomal hydroxylating system. http://purl.uniprot.org/mim/207410 http://purl.uniprot.org/mim/201750 FAD NADPH--cytochrome-c2 reductase NADPH + 2 ferricytochrome c2 = NADP(+) + H(+) + 2 ferrocytochrome c2. FAD Leghemoglobin reductase NAD(P)H + 2 ferrileghemoglobin = NAD(P)(+) + 2 ferroleghemoglobin. With a oxygen as acceptor Thyroid oxidase 2 THOX2 Dual oxidase ThOX Thyroid oxidase Thyroid NADPH oxidase NAD(P)H oxidase NAD(P)H + O(2) = NAD(P)(+) + H(2)O(2). http://purl.uniprot.org/mim/607200 FAD Heme Calcium This flavoprotein is expressed at the apical membrane of thyrocytes, and provides H(2)O(2) for the thyroid peroxidase-catalyzed biosynthesis of thyroid hormones. The electron bridge within the enzyme contains one molecule of FAD and probably two heme groups. When calcium is present, this transmembrane glycoprotein generates H(2)O(2) by transfering electrons from intracellular NAD(P)H to extracellular molecular oxygen. With a quinone or similar compound as acceptor DT-diaphorase Reduced nicotinamide-adenine dinucleotide (phosphate) dehydrogenase Flavoprotein NAD(P)H-quinone reductase p-benzoquinone reductase Naphthoquinone reductase Phylloquinone reductase NADH-menadione reductase Quinone reductase Reduced NAD(P)H dehydrogenase Viologen accepting pyridine nucleotide oxidoreductase Azoreductase Vitamin K reductase NAD(P)H-quinone oxidoreductase Dehydrogenase, reduced nicotinamide adenine dinucleotide (phosphate, quinone) NAD(P)H-quinone dehydrogenase NAD(P)H: menadione oxidoreductase Vitamin-K reductase Menadione reductase Diaphorase NAD(P)H(2) dehydrogenase (quinone) Menadione oxidoreductase NAD(P)H:(quinone-acceptor)oxidoreductase NAD(P)H menadione reductase NAD(P)H dehydrogenase (quinone) NAD(P)H dehydrogenase FAD The enzyme catalyzes a two-electron reduction and has a preference for short-chain acceptor quinones, such as ubiquinone, benzoquinone, juglone and duroquinone. The animal, but not the plant, form of the enzyme is inhibited by dicoumarol. NAD(P)H + a quinone = NAD(P)(+) + a hydroquinone. NADH-Q6 oxidoreductase Reduced nicotinamide adenine dinucleotide-coenzyme Q reductase Coenzyme Q reductase Mitochondrial electron transport complex 1 Type 1 dehydrogenase NADH-CoQ oxidoreductase NADH-ubiquinone-1 reductase Complex 1 dehydrogenase Complex I (mitochondrial electron transport) Complex I (electron transport chain) NADH coenzyme Q1 reductase NADH-ubiquinone oxidoreductase Electron transfer complex I DPNH-ubiquinone reductase NADH-ubiquinone reductase Mitochondrial electron transport complex I Ubiquinone reductase NADH:ubiquinone oxidoreductase complex NADH-CoQ reductase Complex I (NADH:Q1 oxidoreductase) NADH-coenzyme Q oxidoreductase NADH-coenzyme Q reductase Dihydronicotinamide adenine dinucleotide-coenzyme Q reductase NADH dehydrogenase (ubiquinone) DPNH-coenzyme Q reductase http://purl.uniprot.org/mim/256000 The complex, present in mitochondria, can be degraded to form EC 1.6.99.3. http://purl.uniprot.org/mim/502500 http://purl.uniprot.org/mim/535000 http://purl.uniprot.org/mim/540000 FAD http://purl.uniprot.org/mim/252010 http://purl.uniprot.org/mim/500001 NADH + ubiquinone = NAD(+) + ubiquinol. Iron-sulfur Monodehydroascorbate reductase (NADH) NADH + 2 monodehydroascorbate = NAD(+) + 2 ascorbate. NADPH:quinone reductase Zeta-crystallin Quinone oxidoreductase Zinc Specific for NADPH. NADPH + quinone = NADP(+) + semiquinone. Catalyzes the one-electron reduction of certain quinones; orthoquinones are the best substrates. Abundant in the lens of the eye of some mammalian species. Dicoumarol (cf. EC 1.6.5.2) and nitrofurantoin are competitive inhibitors with respect to the quinone substrate. p-benzoquinone reductase (NADPH) Involved in the 4-nitrophenol degradation pathway in bacteria. NADPH + p-benzoquinone = NADP(+) + hydroquinone. 2-hydroxy-1,4-benzoquinone reductase Hydroxybenzoquinone reductase The enzyme differs in substrate speificity from other quinone reductases. The enzyme in Burkholderia cepacia is inducible by 2,4,5-trichlorophenoxyacetate. FMN 2-hydroxy-1,4-benzoquinone + NADH = 1,2,4-trihydroxybenzene + NAD(+). With a nitrogenous group as acceptor Trimethylamine-N-oxide reductase Trimethylamine oxidase NADH + trimethylamine N-oxide = NAD(+) + trimethylamine + H(2)O. With other acceptors NADPH dehydrogenase NADPH diaphorase NADPH + acceptor = NADP(+) + reduced acceptor. FMN or FAD FMN in yeasts; FAD in plants. NADH:cytochrome c oxidoreductase Dihydrocodehydrogenase I dehydrogenase NADH diaphorase NADH dehydrogenase NADH oxidoreductase Reduced diphosphopyridine nucleotide diaphorase Dihydronicotinamide adenine dinucleotide dehydrogenase Diphosphopyrinase NADH-menadione oxidoreductase NADH hydrogenase Diaphorase Cytochrome c reductase Type I dehydrogenase Type 1 dehydrogenase DPNH diaphorase Beta-NADH dehydrogenase dinucleotide Flavoprotein Iron-sulfur Under normal conditions, two protons are extruded from the cytoplasm or the intramitochondrial or stromal compartment. NADH + acceptor = NAD(+) + reduced acceptor. Present in a mitochondrial complex as EC 1.6.5.3. After preparations have been subjected to certain treatments cytochrome c may act as acceptor. NADH dehydrogenase (quinone) Inhibited by AMP and 2,4-dinitrophenol but not by dicoumarol or folic acid derivatives. NADH + acceptor = NAD(+) + reduced acceptor. Menaquinone or other quinones can act as acceptor. NADPH dehydrogenase (quinone) NADPH + acceptor = NADP(+) + reduced acceptor. Menaquinone can act as acceptor. Flavoprotein Inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol. Acting on other nitrogenous compounds as donors With NAD(+) or NADP(+) as acceptor Nitrate reductase (NADH(2)) Assimilatory nitrate reductase NADH-nitrate reductase Nitrate reductase (NADH) NADH-dependent nitrate reductase Assimilatory NADH:nitrate reductase NADH:nitrate oxidoreductase Heme Molybdenum Nitrite + NAD(+) + H(2)O = nitrate + NADH. FAD or FMN Ammonium dehydrogenase Hydroxylamine reductase (NADH) NADH:hydroxylamine oxidoreductase NADH-hydroxylamine reductase N-hydroxy amine reductase Hydroxylamine reductase NH(3) + NAD(+) + H(2)O = hydroxylamine + NADH. Also acts on some hydroxamates. 4-(dimethylamino)phenylazoxybenzene reductase Dimethylaminoazobenzene N-oxide reductase N,N-dimethyl-p-aminoazobenzene oxide reductase NADPH:4-(dimethylamino)phenylazoxybenzene oxidoreductase NADPH-dependent DMAB N-oxide reductase 4-(dimethylamino)phenylazobenzene + NADP(+) = 4-(dimethylamino)phenylazoxybenzene + NADPH. N-hydroxy-2-acetylaminofluorene reductase N-hydroxy-2-acetamidofluorene reductase NAD(P)H:N-hydroxy-2-acetamidofluorene N-oxidoreductase 2-acetamidofluorene + NAD(P)(+) + H(2)O = N-hydroxy-2-acetamidofluorene + NAD(P)H. Also acts, more slowly, on N-hydroxy-4-acetamidobiphenyl. PreQ(1) synthase 7-cyano-7-deazaguanine reductase PreQ(0) oxidoreductase PreQ(0) reductase Queosine is found in the wobble position of tRNA(GUN) in eukaryotes and bacteria and is thought to be involved in translational modulation. This enzyme catalyzes one of the early steps in the synthesis of queosine (Q-tRNA), and is followed by the action of EC 2.4.2.29. The reaction occurs in the reverse direction. 7-aminomethyl-7-carbaguanine + 2 NADP(+) = 7-cyano-7-carbaguanine + 2 NADPH. NAD(P)H bispecific nitrate reductase Assimilatory nitrate reductase NAD(P)H-nitrate reductase Nitrate reductase NAD(P)H Nitrate reductase (reduced nicotinamide adenine dinucleotide (phosphate)) NAD(P)H:nitrate oxidoreductase Assimilatory NAD(P)H-nitrate reductase Nitrate reductase (NAD(P)H) FAD or FMN Molybdenum Heme Nitrite + NAD(P)(+) + H(2)O = nitrate + NAD(P)H. Nitrate reductase (NADPH) Assimilatory NADPH-nitrate reductase Nitrate reductase (NADPH(2)) NADPH:nitrate reductase NADPH:nitrate oxidoreductase NADPH-nitrate reductase Assimilatory nitrate reductase Assimilatory reduced nicotinamide adenine dinucleotide phosphate-nitrate reductase Triphosphopyridine nucleotide-nitrate reductase FAD Nitrite + NADP(+) + H(2)O = nitrate + NADPH. Iron-sulfur Molybdenum Heme Nitrite reductase (NAD(P)H) Nitrite reductase (reduced nicotinamide adenine dinucleotide (phosphate)) Assimilatory nitrite reductase NADH-nitrite oxidoreductase NADPH-nitrite reductase NAD(P)H:nitrite oxidoreductase Iron FAD Iron-sulfur Ammonium hydroxide + 3 NAD(P)(+) + H(2)O = nitrite + 3 NAD(P)H. Siroheme NADH:hyponitrite oxidoreductase Hyponitrite reductase Metal ions 2 hydroxylamine + 2 NAD(+) = hyponitrous acid + 2 NADH. p-aminoazobenzene reductase Orange II azoreductase Dimethylaminobenzene reductase N,N-dimethyl-4-phenylazoaniline azoreductase Orange I azoreductase Dibromopropylaminophenylazobenzoic azoreductase Azo reductase NADPH:4-(dimethylamino)azobenzene oxidoreductase Nicotinamide adenine dinucleotide (phosphate) azoreductase NADPH-dependent azoreductase Methyl red azoreductase NAD(P)H:1-(4'-sulfophenylazo)-2-naphthol oxidoreductase New coccine (NC)-reductase p-dimethylaminoazobenzene azoreductase Azo-dye reductase Azoreductase Azobenzene reductase NC-reductase N,N-dimethyl-1,4-phenylenediamine + aniline + NADP(+) = 4-(dimethylamino)azobenzene + NADPH. Guanosine 5'-monophosphate oxidoreductase Guanosine monophosphate reductase Guanosine 5'-monophosphate reductase Guanosine 5'-phosphate reductase GMP reductase NADPH:GMP oxidoreductase (deaminating) NADPH:guanosine-5'-phosphate oxidoreductase (deaminating) Guanylate reductase Inosine 5'-phosphate + NH(3) + NADP(+) = guanosine 5'-phosphate + NADPH. NAD(P)H:4-nitroquinoline-N-oxide oxidoreductase 4NQO reductase 4-nitroquinoline 1-oxide reductase Nitroquinoline-N-oxide reductase 4-(hydroxyamino)quinoline N-oxide + 2 NAD(P)(+) + H(2)O = 4-nitroquinoline N-oxide + 2 NAD(P)H. With a cytochrome as acceptor Hydroxylamine (acceptor) reductase Cytochrome cd1 Nitrite reductase (cytochrome) Nitrite reductase cd-cytochrome nitrite reductase Methyl viologen-nitrite reductase Nitrite reductase (NO-forming) Cytochrome cd Nitrite reductase (cytochrome; NO-forming) Cytochrome c-551:O(2), NO(2)(+) oxidoreductase Pseudomonas cytochrome oxidase One type comprises proteins containing multiple copper centers, the other a heme protein, cytochrome cd1. FAD Nitric oxide + H(2)O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H(+). Cytochrome cd1 also has oxidase and hydroxylamine reductase activities. The reaction is catalyzed by two types of enzymes, found in the perimplasm of denitrifying bacteria. Acceptors include c-type cytochromes such as cytochrome c-550 or cytochrome c-551 from Paracoccus denitrificans or Pseudomonas aeruginosa, and small blue copper proteins such as azurin and pseudoazurin. May also catalyze the reaction of EC 1.7.99.1 since this is a well-known activity of cytochrome cd1. Copper or iron Cytochrome c nitrite reductase Cytochrome c552 Multiheme nitrite reductase Nitrite reductase (cytochrome; ammonia-forming) Heme The enzyme also reduces nitric oxide and hydroxylamine to ammonia, and sulfite to sulfide. NH(3) + 2 H(2)O + 6 ferricytochrome c = nitrite + 6 ferrocytochrome c + 7 H(+). Calcium TMAO reductase Trimethylamine-N-oxide reductase (cytochrome c) TOR The cytochrome c involved in photosynthetic bacteria is a pentaheme protein. Trimethylamine + 2 (ferricytochrome c)-subunit + H(2)O = trimethylamine N-oxide + 2 (ferrocytochrome c)-subunit + 2 H(+). The reductant is a membrane-bound multiheme cytochrome c. Also reduces dimethyl sulfoxide to dimethyl sulfide. Bis(molybdopterin guanine dinucleotide)molybdenum cofactor With oxygen as acceptor NAO Nitroalkane oxidase Nitroethane oxidase Nitroethane reductase A nitroalkane + H(2)O + O(2) = an aldehyde + nitrite + H(2)O(2). While nitroethane may be the physiological substrate, the enzyme also acts on several other nitroalkanes, including 1-nitropropane, 2-nitropropane, 1-nitrobutane, 1-nitropentane, 1-nitrohexane, nitrocyclohexane and some nitroalkanols. Differs from EC 1.13.11.32 in that the preferred substrates are neutral nitroalkanes rather than anionic nitronates. FAD Acetylindoxyl oxidase N-acetylindoxyl + O(2) = N-acetylisatin + H(2)O. Uric acid oxidase Urate oxidase Uricase II Uricase The 5-hydroxyisourate formed decomposes spontaneously to form allantoin and CO(2), although there is an enzyme-catalyzed pathway in which EC 3.5.2.17 catalyzes the first step. Was previously thought to be a copper protein, but it is now known that the enzymes from soybean (Glycine max), the mold Aspergillus flavus and Bacillus subtilis contains no copper nor any other transition-metal ion. Urate + O(2) + H(2)O = 5-hydroxyisourate + H(2)O(2). Hydroxylamine oxidase Heme Hydroxylamine + O(2) = nitrite + H(2)O. Hemoprotein with 7 c-type hemes and one P-460-type heme per subunit. 3-aci-nitropropanoate oxidase 3-aci-nitropropanoate + O(2) = 3-oxopropanoate + nitrite + H(2)O(2). FMN The primary products of the enzymatic reaction are probably the nitropropanoate free radical and superoxide. Also acts, more slowly, on 4-aci-nitrobutanoate. With an iron-sulfur protein as acceptor Ferredoxin--nitrite reductase Iron-sulfur Siroheme NH(3) + 2 H(2)O + 6 oxidized ferredoxin = nitrite + 6 reduced ferredoxin + 7 H(+). Assimilatory nitrate reductase Ferredoxin--nitrate reductase Iron-sulfur Nitrite + H(2)O + 2 oxidized ferredoxin = nitrate + 2 reduced ferredoxin + 2 H(+). Molybdenum With other acceptors Hydroxylamine reductase Hydroxylamine (acceptor) reductase May be identical to EC 1.7.2.1. Reduced pyocyanine, methylene blue and flavins act as donors for the reduction of hydroxylamine. NH(3) + H(2)O + acceptor = hydroxylamine + reduced acceptor. Flavoprotein Nitrate reductase Respiratory nitrate reductase Nitrite + acceptor = nitrate + reduced acceptor. Reduced benzyl viologen and other dyes bring about the reduction of nitrate. The Pseudomonas enzyme is a cytochrome, but the enzyme from Micrococcus halodenitrificans is an iron protein containing molybdenum. Nitrous-oxide reductase Copper Reduced viologens or methylene blue act as donors for the reduction of nitrous oxide. N(2) + H(2)O + acceptor = N(2)O + reduced acceptor. Nitric-oxide reductase Nitrous oxide + acceptor + H(2)O = 2 nitric oxide + reduced acceptor. Phenazine methosulfate can act as acceptor. A heterodimer of cytochromes b and c. Hydroxylamine oxidoreductase (1) Hydroxylamine + NH(3) = hydrazine + H(2)O. Ferricyanide, phenazine methosulfate and methylthiazolyltetrazolium bromide can act as acceptors in this 4-electron transfer reaction. The enzyme from anammox bacteria is inhibited by phosphate, oxygen and high nitrite concentrations and is also capable of reducing NO to N(2)O. (2) Hydrazine + acceptor = N(2) + reduced acceptor. Acting on a sulfur group of donors With NAD(+) or NADP(+) as acceptor CoA-glutathione reductase Coenzyme A glutathione disulfide reductase NADPH:CoA-glutathione oxidoreductase CoA-glutathione reductase (NADPH) Coenzyme A disulfide-glutathione reductase NADPH-dependent coenzyme A-SS-glutathione reductase Flavoprotein The substrate is a mixed disulfide. CoA + glutathione + NADP(+) = CoA-glutathione + NADPH. May be identical to EC 1.8.1.9. Asparagusic dehydrogenase NADH:asparagusate oxidoreductase Asparagusate reductase (NADH) Asparagusate reductase Asparagusate dehydrogenase Also acts on lipoate. 3-mercapto-2-mercaptomethylpropanoate + NAD(+) = asparagusate + NADH. Trypanothione reductase NADPH:trypanothione oxidoreductase N(1),N(8)-bis(glutathionyl)spermidine reductase Trypanothione-disulfide reductase Trypanothione + NADP(+) = trypanothione disulfide + NADPH. The activity is dependent on a redox-active cystine at the active center (cf. EC 1.8.1.7). FAD Trypanothione disulfide is the oxidized form of N(1),N(8)-bis(glutathionyl)-spermidine from the insect-parasitic trypanosomatid Crithidia fasciculata. Bis-gamma-glutamylcystine reductase NADPH:bis-gamma-glutamylcysteine oxidoreductase Bis-gamma-glutamylcystine reductase (NADPH) Highly specific. 2 gamma-glutamylcysteine + NADP(+) = bis-gamma-glutamylcystine + NADPH. Not identical with EC 1.8.1.7 or EC 1.8.1.14. CoADR Coenzyme A disulfide reductase CoA-disulfide reductase CoA-disulfide reductase (NAD(P)H) NADH:CoA-disulfide oxidoreductase FAD Not identical with EC 1.8.1.6, EC 1.8.1.7, or EC 1.8.1.13. 2 CoA + NAD(P)(+) = CoA-disulfide + NAD(P)H. While the enzyme from Staphylococcus aureus has a strong preference for NADPH, that from the thermophilic archaea Pyrococcus horikoshii can use both NADH and NADPH efficiently. Mycothione reductase Mycothiol-disulfide reductase No activity with glutathione, trypanothione or coenzyme A as substrate. 2 mycothiol + NAD(P)(+) = mycothione + NAD(P)H. FAD Sulfite reductase (NADPH) FMN Heme FAD H(2)S + 3 NADP(+) + 3 H(2)O = sulfite + 3 NADPH. Hypotaurine dehydrogenase Molybdenum Heme Hypotaurine + H(2)O + NAD(+) = taurine + NADH. Diaphorase L-protein Lipoamide reductase (NADH) Dehydrolipoate dehydrogenase Lipoic acid dehydrogenase Dihydrothioctic dehydrogenase Dihydrolipoic dehydrogenase E3 component of alpha-ketoacid dehydrogenase complexes LDP-Glc Lipoyl dehydrogenase Lipoamide reductase Lipoamide oxidoreductase (NADH) Lipoamide dehydrogenase (NADH) LDP-Val Lipoate dehydrogenase Glycine-cleavage system L-protein Dihydrolipoyl dehydrogenase Dihydrolipoamide dehydrogenase A component of the multienzyme 2-oxo-acid dehydrogenase complexes. Protein N(6)-(dihydrolipoyl)lysine + NAD(+) = protein N(6)-(lipoyl)lysine + NADH. http://purl.uniprot.org/mim/248600 It plays a similar role in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is the dihydrolipoyl group in the H-protein of the glycine-cleavage system, in which it acts, together with EC 1.4.4.2 and EC 2.1.2.10 to break down glycine. Was first shown to catalyze the oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein. FAD In the pyruvate dehydrogenase complex, it binds to the core of EC 2.3.1.12 and catalyzes oxidation of its dihydrolipoyl groups. It can also use free dihydrolipoate, dihydrolipoamide or dihydrolipoyllysine as substrate. 2-KPCC NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase 2-oxopropyl-CoM reductase (carboxylating) NADPH:2-(2-ketopropylthio)ethanesulfonate oxidoreductase/carboxylase Also acts on thioethers longer in chain length on the oxo side, e.g. 2-oxobutyl-CoM, but this portion must be attached to CoM (2-mercaptoethanesulfonate); no CoM analogs will substitute. 2-mercaptoethanesulfonate + acetoacetate + NADP(+) = 2-(2-oxopropylthio)ethanesulfonate + CO(2) + NADPH. Forms component II of a four-component enzyme system (comprising EC 4.4.1.23 (component I), EC 1.8.1.5 (component II), EC 1.1.1.268 (component III) and EC 1.1.1.269 (component IV)) that is involved in epoxyalkane carboxylation in Xanthobacter sp. strain Py2. Cystine reductase NADH:L-cystine oxidoreductase NADH-dependent cystine reductase Cystine reductase (NADH) 2 L-cysteine + NAD(+) = L-cystine + NADH. GSH reductase Glutathione-disulfide reductase NADPH:oxidized-glutathione oxidoreductase Glutathione reductase NADPH-GSSG reductase NADPH-glutathione reductase GSSG reductase Glutathione reductase (NADPH) Glutathione S-reductase Activity is dependent on a redox-active disulfide in each of the active centers. http://purl.uniprot.org/mim/138300 2 glutathione + NADP(+) = glutathione disulfide + NADPH. FAD Protein-disulfide reductase Protein disulfide reductase Disulfide reductase NAD(P)H:protein-disulfide oxidoreductase Insulin-glutathione transhydrogenase Protein dithiol + NAD(P)(+) = protein disulfide + NAD(P)H. NADPH--thioredoxin reductase Thioredoxin reductase (NADPH) NADPH:oxidized thioredoxin oxidoreductase Thioredoxin-disulfide reductase NADP--thioredoxin reductase May be identical to EC 1.8.1.10. Thioredoxin + NADP(+) = thioredoxin disulfide + NADPH. With a cytochrome as acceptor Sulfite dehydrogenase Associated with cytochrome c-551. Sulfite + 2 ferricytochrome c + H(2)O = sulfate + 2 ferrocytochrome c + 2 H(+). Thiosulfate dehydrogenase Tetrathionate synthase 2 thiosulfate + 2 ferricytochrome c = tetrathionate + 2 ferrocytochrome c. With oxygen as acceptor Sulfite oxidase Heme http://purl.uniprot.org/mim/272300 Sulfite + O(2) + H(2)O = sulfate + H(2)O(2). Molybdenum Thiol oxidase Sulfhydryl oxidase 4 R'C(R)SH + O(2) = 2 R'C(R)S-S(R)CR' + 2 H(2)O. The enzyme is not specific for R'. R may be =S or =O, or a variety of other groups. Glutathione oxidase Also acts, more slowly, on L-cysteine and several other thiols. FAD 2 glutathione + O(2) = glutathione disulfide + H(2)O(2). Methanethiol oxidase Methylmercaptan oxidase Methanethiol + O(2) + H(2)O = formaldehyde + H(2)S + H(2)O(2). Prenylcysteine lyase Prenylcysteine oxidase An S-prenyl-L-cysteine + O(2) + H(2)O = a prenal + L-cysteine + H(2)O(2). FAD Originally thought to be a simple lyase, EC 4.4.1.18. May represent the final step in the degradation of prenylated proteins in mammalian tissues. N-acetyl-prenylcysteine and prenylcysteinyl peptides are not substrates. Cleaves the thioether bond of S-prenyl-L-cysteines, such as S-farnesylcysteine and S-geranylgeranylcysteine. With a disulfide as acceptor Glutathione--homocystine transhydrogenase 2 glutathione + homocystine = glutathione disulfide + 2 homocysteine. The reactions catalyzed by this enzyme and by others in this subclass may be similar to those catalyzed by EC 2.5.1.18. Adenylyl-sulfate reductase (thioredoxin) Thioredoxin-dependent 5'-adenylylsulfate reductase AMP + sulfite + thioredoxin disulfide = 5'-adenylyl sulfate + thioredoxin. Uses thioredoxin as electron donor, not glutathione or other donors, distinguishing it from EC 1.8.4.9 and EC 1.8.99.2. Uses adenylyl sulfate, not phosphoadenylyl sulfate, distinguishing this enzyme from EC 1.8.4.8. Methionine sulfoxide reductase Peptide methionine sulfoxide reductase Methionine S-oxide reductase (S-form oxidizing) Peptide-methionine-(S)-S-oxide reductase Methionine S-oxide reductase Peptide Met(O) reductase Methionine sulfoxide reductase A Methionine sulphoxide reductase A (1) Peptide-L-methionine + thioredoxin disulfide + H(2)O = peptide-L-methionine (S)-S-oxide + thioredoxin. The reaction proceeds via a sulfenic-acid intermediate. On the free amino acid, it can also reduce D-methionine (S)-S-oxide but more slowly. Plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. (2) L-methionine + thioredoxin disulfide + H(2)O = L-methionine (S)-S-oxide + thioredoxin. Exhibits high specificity for the reduction of the S-form of L-methionine S-oxide, acting faster on the residue in a peptide than on the free amino acid. The reaction occurs in the reverse direction to that shown above. Methionine sulfoxide reductase Methionine sulfoxide reductase B Methionine S-oxide reductase (R-form oxidizing) Methionine S-oxide reductase Selenoprotein R Peptide-methionine (R)-S-oxide reductase The reaction occurs in the reverse direction to that shown above. For MsrB2 and MsrB3, thioredoxin is a poor reducing agent but thionein works well. Exhibits high specificity for reduction of the R-form of methionine S-oxide, with higher activity being observed with L-methionine S-oxide than with D-methionine S-oxide. Plays a role in preventing oxidative-stress damage caused by reactive oxygen species by reducing the oxidized form of methionine back to methionine and thereby reactivating peptides that had been damaged. Selenium Zinc The reaction proceeds via a sulfenic-acid intermediate. While both free and protein-bound methionine (R)-S-oxide act as substrates, the activity with the peptide-bound form is far greater. Peptide-L-methionine + thioredoxin disulfide + H(2)O = peptide-L-methionine (R)-S-oxide + thioredoxin. Acetylmethionine sulfoxide reductase Methionine sulfoxide reductase Methionine-S-oxide reductase Methyl sulfoxide reductase I and II L-methionine-(S)-S-oxide reductase FSMsr Free-methionine (S)-S-oxide reductase Dithiothreitol can replace reduced thioredoxin. NADPH The reaction occurs in the opposite direction to that given above. L-methionine + thioredoxin disulfide + H(2)O = L-methionine (S)-S-oxide + thioredoxin. L-methionine (R)-S-oxide is not a substrate (see EC 1.8.4.14). Free met-R-(o) reductase FRMsr L-methionine-(R)-S-oxide reductase Free-methionine (R)-S-oxide reductase L-methionine + thioredoxin disulfide + H(2)O = L-methionine (R)-S-oxide + thioredoxin. Unlike EC 1.8.4.12 this enzyme cannot use peptide-bound methionine (R)-S-oxide as a substrate. Differs from EC 1.8.4.13, in that L-methionine (S)-S-oxide is not a substrate. NADPH Insulin reductase Protein-disulfide reductase (glutathione) Glutathione--insulin transhydrogenase Reduces insulin and some other proteins. 2 glutathione + protein-disulfide = glutathione disulfide + protein-dithiol. Glutathione--CoA-glutathione transhydrogenase CoA + glutathione disulfide = CoA-glutathione + glutathione. Glutathione--cystine transhydrogenase 2 glutathione + cystine = oxidized glutathione + 2 cysteine. Glutathione-dependent thiol:disulfide oxidoreductase Enzyme-thiol transhydrogenase (oxidized-glutathione) [Xanthine-dehydrogenase]:oxidized-glutathione S-oxidoreductase Thiol:disulfide oxidoreductase Enzyme-thiol transhydrogenase (glutathione-disulfide) Also reduces the disulfide bond of ricin. Not inhibited by Cu(2+) or thiol reagents. [Xanthine dehydrogenase] + glutathione disulfide = [xanthine oxidase] + 2 glutathione. Converts EC 1.17.1.4 into EC 1.17.3.2 in the presence of glutathione disulfide. 3'-phosphoadenylylsulfate reductase Phosphoadenosine-phosphosulfate reductase Thioredoxin:3'-phospho-adenylylsulfate reductase PAdoPS reductase Phosphoadenylyl-sulfate reductase (thioredoxin) Thioredoxin:adenosine 3'-phosphate 5'-phosphosulfate reductase PAPS sulfotransferase PAPS reductase PAPS reductase, thioredoxin-dependent Adenosine 3',5'-bisphosphate + sulfite + thioredoxin disulfide = 3'-phosphoadenylyl sulfate + thioredoxin. Specific for PAPS. The enzyme from Escherichia coli will use thioredoxins from other species. Adenylyl-sulfate reductase (glutathione) AMP,sulfite:oxidized-glutathione oxidoreductase (adenosine-5'-phosphosulfate-forming) 5'-adenylylsulfate reductase Plant-type 5'-adenylylsulfate reductase AMP + sulfite + glutathione disulfide = adenylyl sulfate + 2 glutathione. Glutathione can be replaced by gamma-glutamylcysteine or dithiothreitol, but not by thioredoxin, glutaredoxin or mercaptoethanol. The enzyme from Arabidopsis thaliana contains a glutaredoxin-like domain. Also found in other photosynthetic eukaryotes, e.g., the Madagascar periwinkle, Catharanthus roseus and the hollow green seaweed, Enteromorpha intestinalis. Differs from EC 1.8.99.2, in using glutathione as the reductant. With a quinone or similar compound as acceptor Glutathione dehydrogenase (ascorbate) 2 glutathione + dehydroascorbate = glutathione disulfide + ascorbate. Thiosulfate:quinone oxidoreductase Thiosulfate dehydrogenase (quinone) TQO Thiosulfate oxidoreductase, tetrathionate-forming Unlike EC 1.8.2.2, this enzyme cannot utilize cytochrome c as an acceptor. The reaction can also proceed with ferricyanide as the electron acceptor, but more slowly. 2 thiosulfate + 2 6-decylubiquinone = tetrathionate + 2 6-decylubiquinol. With an iron-sulfur protein as acceptor Sulfite reductase (ferredoxin) Iron H(2)S + 3 oxidized ferredoxin + 6 H(2)O = sulfite + 6 reduced ferredoxin + 6 H(+). With other, known, acceptors CoB--CoM heterodisulfide reductase Soluble heterodisulfide reductase Heterodisulfide reductase Coenzyme B + coenzyme M + methanophenazine = N-(7-((2-sulfoethyl)dithio)heptanoyl)-O(3)-phospho-L-threonine + dihydromethanophenazine. Found in methanogenic archaea, particularly Methanosarcina species, and regenerates coenzyme M and coenzyme B after the action of EC 2.8.4.1. Highly specific for both coenzyme M and coenzyme B. Reacts with various phenazine derivatives, including 2-hydroxyphenazine and 2-bromophenazine. Heme Iron-sulfur Peroxiredoxin-(S-hydroxy-S-oxocysteine) reductase Sulfiredoxin Occasionally the S-hydroxycysteine residue is further oxidized to the sulfinic acid S-hydroxy-S-oxocysteine, thereby inactivating the enzyme. Peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH = peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R. Attack by a thiol splits this bond, leaving the peroxiredoxin as the sulfenic acid and the reductase as the thiol. The reductase provides a mechanism for regenerating the active form of peroxiredoxin, i.e. the peroxiredoxin-(S-hydroxycysteine) form. In the course of the reaction of EC 1.11.1.15, its cysteine residue is alternately oxidized to the sulfenic acid, S-hydroxycysteine, and reduced back to cysteine. Apparently the reductase first catalyzes the phosphorylation of the -S(O)-OH group by ATP to give -S(O)-O-P, which is attached to the peroxiredoxin by a cysteine residue, forming an -S(O)-S-link between the two enzymes. With other acceptors Sulfite reductase Iron H(2)S + acceptor + 3 H(2)O = SO(3)(2-) + reduced acceptor. A stoichiometry of six molecules of reduced methyl viologen per molecule of sulfide formed was found. Adenylyl-sulfate reductase Methyl viologen can act as acceptor. Iron FAD AMP + sulfite + acceptor = adenylyl sulfate + reduced acceptor. Desulfoviridin Desulforubidin Desulfofuscidin Hydrogensulfite reductase Bisulfite reductase Dissimilatory sulfite reductase Iron-sulfur (O(3)S.S.SO(3))(2-) + acceptor + 2 H(2)O + OH(-) = 3 HSO(3)(-) + reduced acceptor. Methyl viologen can act as acceptor. Siroheme A group of sirohemoproteins containing iron-sulfur centers (P-582). Acting on a heme group of donors With oxygen as acceptor Cytochrome-c oxidase Warburg's respiratory enzyme Cytochrome oxidase Cytochrome aa3 Complex IV (mitochondrial electron transport) Cytochrome a3 Copper The reduction of O(2) to water is accompanied by the extrusion of four protons from the intramitochondrial compartment. Several bacteria appear to contain analogous oxidases. http://purl.uniprot.org/mim/535000 4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O. http://purl.uniprot.org/mim/220110 With a nitrogenous group as acceptor Nitrate reductase (cytochrome) 2 ferrocytochrome + nitrate + 2 H(+) = 2 ferricytochrome + nitrite. With other acceptors Iron--cytochrome-c reductase Iron Ferrocytochrome c + Fe(3+) = ferricytochrome c + Fe(2+). Other oxidoreductases Sole sub-subclass for oxidoreductases that do not belong in the other subclasses Chlorate reductase AH(2) + chlorate = A + H(2)O + chlorite. Flavins or benzylviologen can act as acceptor. Type II iodothyronine deiodinase L-thyroxine iodohydrolase (reducing) Iodothyronine 5'-deiodinase Diiodothyronine 5'-deiodinase Thyroxine 5-deiodinase Iodothyronine outer ring monodeiodinase Thyroxine 5'-deiodinase Type I iodothyronine deiodinase The enzyme consists of type I and type II enzymes, both containing selenocysteine, but with different kinetics. The enzyme activity has only been demonstrated in the direction of 5'-deiodination, which renders the thyroid hormone more active. For the type I enzyme the first reaction is a reductive deiodination converting the -Se-H group of the enzyme into an -Se-I group; the reductant then reconverts this into -Se-H, releasing iodide. 3,5,3'-triiodo-L-thyronine + iodide + A + H(+) = L-thyroxine + AH(2). http://purl.uniprot.org/mim/147892 Iodothyronine 5-deiodinase Thyroxine 5-deiodinase Type III iodothyronine deiodinase Iodothyronine inner ring monodeiodinase Diiodothyronine 5'-deiodinase This removal of the 5-iodine, i.e. from the inner ring, largely inactivates the hormone thyroxine. 3,3',5'-triiodo-L-thyronine + iodide + A + H(+) = L-thyroxine + AH(2). The enzyme activity has only been demonstrated in the direction of 5-deiodination. Pyrogallol hydroxytransferase Transhydroxylase Pyrogallol hydroxyltransferase 1,2,3,5-tetrahydroxybenzene + 1,2,3-trihydroxybenzene = 1,3,5-trihydroxybenzene + 1,2,3,5-tetrahydroxybenzene. 1,2,3,5-tetrahydroxybenzene acts as a cosubstrate for the conversion of pyrogallol into phloroglucinol, and for a number of similar isomerizations. Molybdenum The enzyme is provisionally listed here, but might be considered as the basis for a new class in the transferases, analogous to the aminotransferases. Sulfur reductase Reduction of elemental sulfur or polysulfide to H(2)S. Sulfur can be reduced with hydrogen as donor in the presence of hydrogenase, or by photochemical reduction in the presence of phenosafranin. Formate acetyltransferase-glycine dihydroflavodoxin:S-adenosyl-L-methionine oxidoreductase (S-adenosyl-L-methionine cleaving) Formate acetyltransferase activating enzyme [Formate-C-acetyltransferase]-activating enzyme [Pyruvate formate-lyase]-activating enzyme PFL activase PFL-glycine:S-adenosyl-L-methionine H transferase (flavodoxin-oxidizing, S-adenosyl-L-methionine-cleaving) Iron-sulfur S-adenosyl-L-methionine + dihydroflavodoxin + [formate C-acetyltransferase]-glycine = 5'-deoxyadenosine + L-methionine + flavodoxin semiquinone + [formate C-acetyltransferase]-glycin-2-yl radical. A single glycine residue in EC 2.3.1.54 is oxidized to the corresponding radical by transfer of H from its CH(2) to AdoMet with concomitant cleavage of the latter. The first stage is reduction of the AdoMet to give methionine and the 5'-deoxyadenosin-5-yl radical, which then abstracts a hydrogen radical from the glycine residue. Tetrachloroethene reductase Tetrachloroethene reductive dehalogenase Although the physiological reductant is unknown, the supply of reductant in some organisms is via reduced menaquinone, itself formed from molecular hydrogen, via EC 1.12.99.3. The reaction occurs in the reverse direction. Trichloroethene + chloride + acceptor = tetrachloroethene + reduced acceptor. This enzyme allows the common pollutant tetrachloroethene to support bacterial growth and is responsible for disposal of a number of chlorinated hydrocarbons by this organism. The enzyme also reduces trichloroethene to dichloroethene. Methyl viologen can act as electron donor. Iron-sulfur Selenate reductase A number of compounds, including acetate, lactate, pyruvate, and certain sugars, amino acids, fatty acids, di-and tricarboxylic acids, and benzoate can serve as electron donors. Molybdenum Heme Selenite + H(2)O + acceptor = selenate + reduced acceptor. Nitrate, nitrite, chlorate and sulfate are not substrates. Iron-sulfur The periplasmic enzyme from Thauera selenatis is a complex comprising three heterologous subunits (alpha, beta and gamma). Transferases Transferring one-carbon groups Methyltransferases Nicotinamide N-methyltransferase S-adenosyl-L-methionine + nicotinamide = S-adenosyl-L-homocysteine + 1-methylnicotinamide. Homocysteine S-methyltransferase The bacterial enzyme uses S-methylmethionine as donor more actively than S-adenosyl-L-methionine. S-adenosyl-L-methionine + L-homocysteine = S-adenosyl-L-homocysteine + L-methionine. Protein-S-isoprenylcysteine O-methyltransferase Isoprenylcysteine carboxylmethyltransferase Prenylcysteine carboxyl methyltransferase Prenylated protein carboxyl methyltransferase C-terminal S-geranylgeranylcysteine and S-geranylcysteine residues are also methylated, more slowly. S-adenosyl-L-methionine + protein C-terminal S-farnesyl-L-cysteine = S-adenosyl-L-homocysteine + protein C-terminal S-farnesyl-L-cysteine methyl ester. Macrocin O-methyltransferase The 3-hydroxyl group of a 2-O-methyl-6-deoxy-D-allose residue in the macrolide antibiotic macrocin acts as methyl acceptor; also converts lactenosin into desmyocin. S-adenosyl-L-methionine + macrocin = S-adenosyl-L-homocysteine + tylosin. Not identical with EC 2.1.1.102. Demethylmacrocin O-methyltransferase The 2-hydroxyl group of a 6-deoxy-D-allose residue in demethylmacrocin acts as methyl acceptor. Not identical with EC 2.1.1.101. S-adenosyl-L-methionine + demethylmacrocin = S-adenosyl-L-homocysteine + macrocin. Phosphoethanolamine N-methyltransferase S-adenosyl-L-methionine + ethanolamine phosphate = S-adenosyl-L-homocysteine + N-methylethanolamine phosphate. The enzyme may catalyze the transfer of two further methyl groups to the product. Caffeoyl-CoA O-methyltransferase Trans-caffeoyl-CoA 3-O-methyltransferase S-adenosyl-L-methionine + caffeoyl-CoA = S-adenosyl-L-homocysteine + feruloyl-CoA. N-benzoyl-4-hydroxyanthranilate 4-O-methyltransferase S-adenosyl-L-methionine + N-benzoyl-4-hydroxyanthranilate = S-adenosyl-L-homocysteine + N-benzoyl-4-methoxyanthranilate. Involved in the biosynthesis of phytoalexins. Tryptophan 2-C-methyltransferase D-tryptophan and (indol-3-yl)pyruvate can also act as acceptors, but more slowly. S-adenosyl-L-methionine + L-tryptophan = S-adenosyl-L-homocysteine + L-2-methyltryptophan. Uroporphyrinogen-III C-methyltransferase Uroporphyrin-III C-methyltransferase SUMT S-adenosyl-L-methionine-dependent uroporphyrinogen III methylase Uroporphyrinogen-III methylase Uroporphyrinogen III methylase Uroporphyrinogen methyltransferase Adenosylmethionine-uroporphyrinogen III methyltransferase Urogen III methylase Uroporphyrinogen-III methyltransferase Also involved in the biosynthesis of cobalamin. This enzyme catalyzes two sequential methylation reactions, the first forming precorrin-1 and the second leading to the formation of precorrin-2. (2) S-adenosyl-L-methionine + precorrin-1 = S-adenosyl-L-homocysteine + precorrin-2. (1) S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1. In some bacteria, steps 1-3 are catalyzed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirA being responsible for the above reaction. The second step involves an NAD(+)-dependent dehydrogenation to form sirohydrochlorin from precorrin-2 (EC 1.3.1.76) and the third step involves the chelation of Fe(2+) to sirohydrochlorin to form siroheme (EC 4.99.1.4). In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. It is the first of three steps leading to the formation of siroheme from uroporphyrinogen III. 6-hydroxymellein O-methyltransferase 6-methoxymellein is a phytoalexin produced by carrot tissue. S-adenosyl-L-methionine + 6-hydroxymellein = S-adenosyl-L-homocysteine + 6-methoxymellein. 3,4-dehydro-6-hydroxymellein can also act as acceptor. Demethylsterigmatocystin 6-O-methyltransferase S-adenosyl-L-methionine + 6-demethylsterigmatocystin = S-adenosyl-L-homocysteine + sterigmatocystin. Involved in the biosynthesis of aflatoxins in fungi. Dihydrodemethylsterigmatocystin can also act as acceptor. Magnesium protoporphyrin IX methyltransferase Mg-protoporphyrin IX methyltransferase S-adenosyl-L-methionine:magnesium-protoporphyrin O-methyltransferase S-adenosyl-L-methionine:Mg protoporphyrin methyltransferase S-adenosylmethionine-magnesium protoporphyrin methyltransferase Magnesium-protoporphyrin O-methyltransferase (-)-S-adenosyl-L-methionine:magnesium-protoporphyrin IX methyltransferase S-adenosylmethioninemagnesium protoporphyrin methyltransferase S-adenosyl-L-methionine + magnesium protoporphyrin IX = S-adenosyl-L-homocysteine + magnesium protoporphyrin IX 13-methyl ester. Sterigmatocystin 7-O-methyltransferase Sterigmatocystin 8-O-methyltransferase O-methyltransferase II S-adenosyl-L-methionine:sterigmatocystin 7-O-methyltransferase Sterigmatocystin methyltransferase S-adenosyl-L-methionine + sterigmatocystin = S-adenosyl-L-homocysteine + 8-O-methylsterigmatocystin. Involved in the biosynthesis of aflatoxins in fungi. Dihydrosterigmatocystin can also act as acceptor. Anthranilate N-methyltransferase S-adenosyl-L-methionine + anthranilate = S-adenosyl-L-homocysteine + N-methylanthranilate. Involved in the biosynthesis of acridine alkaloids in plant tissues. Glucuronoxylan 4-O-methyltransferase S-adenosyl-L-methionine + glucuronoxylan D-glucuronate = S-adenosyl-L-homocysteine + glucuronoxylan 4-O-methyl-D-glucuronate. Restriction-modification system Modification methylase N(4)-cytosine-specific DNA methylase Site-specific DNA-methyltransferase (cytosine-N(4)-specific) This is a large group of enzymes, the majority of which, with enzymes of similar site specificity listed as EC 3.1.21.3, EC 3.1.21.4 and EC 3.1.21.5, form so-called restriction-modification systems. See the REBASE database for a complete list of these enzymes: http://rebase.neb.com/rebase/ S-adenosyl-L-methionine + DNA cytosine = S-adenosyl-L-homocysteine + DNA N(4)-methylcytosine. Hexaprenyldihydroxybenzoate methyltransferase DHHB-Mt DHHB methyltransferase 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase Dihydroxyhexaprenylbenzoate methyltransferase S-adenosyl-L-methionine + 3-hexaprenyl-4,5-dihydroxybenzoate = S-adenosyl-L-homocysteine + 3-hexaprenyl-4-hydroxy-5-methoxybenzoate. Involved in the pathway of ubiquinone synthesis. (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline N-methyltransferase (RS)-tetrahydrobenzylisoquinoline N-methyltransferase Norreticuline N-methyltransferase The physiological substrate is likely to be coclaurine. Broad substrate specificity for (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinolines; including coclaurine, norcoclaurine, isococlaurine, norarmepavine, norreticuline and tetrahydropapaverine. Participates in the pathway leading to benzylisoquinoline alkaloid synthesis in plants. Both R-and S-enantiomers are methylated. However, norreticuline has not been found to occur in nature and that rdfs:label does not reflect the broad specificity of the enzyme for (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinolines. Was earlier termed norreticuline N-methyltransferase. S-adenosyl-L-methionine + (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline = S-adenosyl-L-homocysteine + N-methyl-(RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline. 3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase S-adenosyl-L-methionine + 3'-hydroxy-N-methyl-(S)-coclaurine = S-adenosyl-L-homocysteine + (S)-reticuline. Has also been shown to catalyze the methylation of (RS)-laudanosoline, (S)-3'-hydroxycoclaurine and (RS)-7-O-methylnoraudanosoline. Involved in isoquinoline alkaloid metabolism in plants. (S)-scoulerine 9-O-methyltransferase The product of this reaction is a precursor for protoberberine alkaloids in plants. S-adenosyl-L-methionine + (S)-scoulerine = S-adenosyl-L-homocysteine + (S)-tetrahydrocolumbamine. Columbamine O-methyltransferase Distinct in specificity from EC 2.1.1.88. S-adenosyl-L-methionine + columbamine = S-adenosyl-L-homocysteine + palmatine. The product of this reaction is a protoberberine alkaloid that is widely distributed in the plant kingdom. 10-hydroxydihydrosanguinarine 10-O-methyltransferase S-adenosyl-L-methionine + 10-hydroxydihydrosanguinarine = S-adenosyl-L-homocysteine + dihydrochelirubine. Part of the pathway for synthesis of benzophenanthridine alkaloids in plants. Methionine S-methyltransferase Zinc or manganese S-adenosyl-L-methionine + L-methionine = S-adenosyl-L-homocysteine + S-methyl-L-methionine. 12-hydroxydihydrochelirubine 12-O-methyltransferase S-adenosyl-L-methionine + 12-hydroxydihydrochelirubine = S-adenosyl-L-homocysteine + dihydromacarpine. Part of the pathway for synthesis of benzophenanthridine alkaloid macarpine in plants. 6-O-methylnorlaudanosoline 5'-O-methyltransferase Nororientaline is a precursor of the alkaloid papaverine. S-adenosyl-L-methionine + 6-O-methylnorlaudanosoline = S-adenosyl-L-homocysteine + nororientaline. Tetrahydroprotoberberine cis-N-methyltransferase (S)-tetrahydroprotoberberine N-methyltransferase Involved in the biosynthesis of isoquinoline alkaloids in plants. S-adenosyl-L-methionine + (S)-7,8,13,14-tetrahydroprotoberberine = S-adenosyl-L-homocysteine + cis-N-methyl-(S)-7,8,13,14-tetrahydroprotoberberine. [Cytochrome c]-methionine S-methyltransferase S-adenosyl-L-methionine + [cytochrome c]-methionine = S-adenosyl-L-homocysteine + [cytochrome c]-S-methyl-methionine. [Cytochrome c]-arginine N-methyltransferase S-adenosyl-L-methionine + [cytochrome c]-arginine = S-adenosyl-L-homocysteine + [cytochrome c]-N(omega)-methyl-arginine. Histone-arginine N-methyltransferase Protein-arginine N-methyltransferase Histone protein methylase Protein methylase I The rdfs:label protein methylase I is misleading since it has been used for a number of enzymes with different specificities. S-adenosyl-L-methionine + histone-arginine = S-adenosyl-L-homocysteine + histone-N(omega)-methyl-arginine. Forms the N(omega)-monomethyl-and N(omega),N(omega')-dimethyl, but not the N(omega),N(omega)-dimethyl-arginine derivatives. Protein methylase I Protein-arginine N-methyltransferase Myelin basic protein methylase [Myelin basic protein]-arginine N-methyltransferase S-adenosyl-L-methionine + [myelin basic protein]-arginine = S-adenosyl-L-homocysteine + [myelin basic protein]-N(omega)-methyl-arginine. Forms the N(omega)-monomethyl-, N(omega),N(omega)-dimethyl-and N(omega),N(omega')-dimethyl-arginine derivatives. The rdfs:label protein methylase I is misleading since it has been used for a number of enzymes with different specificities. RuBisCO LSMT [Ribulose-bisphosphate carboxylase]-lysine N-methyltransferase Ribulose-bisphosphate-carboxylase/oxygenase N-methyltransferase RuBisCO methyltransferase The enzyme methylates Lys-14 in the large subunits of hexadecameric higher plant EC 4.1.1.39. S-adenosyl-L-methionine + [ribulose-1,5-bisphosphate carboxylase]-lysine = S-adenosyl-L-homocysteine + [ribulose-1,5-bisphosphate carboxylase]-N(6)-methyl-L-lysine. (RS)-norcoclaurine 6-O-methyltransferase The enzyme will also catalyze the 6-O-methylation of (RS)-norlaudanosoline to form 6-O-methyl-norlaudanosoline, but this alkaloid has not been found to occur in plants. Norcoclaurine is 6,7-dihydroxy-1-((4-hydroxyphenyl)methyl)-1,2,3,4-tetrahydroisoquinoline. S-adenosyl-L-methionine + (RS)-norcoclaurine = S-adenosyl-L-homocysteine + (RS)-coclaurine. Myo-inositol 4-O-methyltransferase Myo-inositol 6-O-methyltransferase S-adenosyl-L-methionine:myo-inositol 4-O-methyltransferase Inositol 4-methyltransferase The enzyme also methylates 1L-1,2,4/3,5-cyclohexanepentol, 2,4,6/3,5-pentahydroxycyclohexanone, D,L-2,3,4,6/5-pentacyclohexanone and 2,2'-anhydro-2-C-hydroxymethyl-myo-inositol, but at lower rates than that of myo-inositol. The enzyme from Vigna umbellata is highly specific for S-adenosyl-L-methionine. S-adenosyl-L-methionine + myo-inositol = S-adenosyl-L-homocysteine + 1D-4-O-methyl-myo-inositol. Methyltetrahydrofolate--homocysteine vitamin B12 methyltransferase 5-methyltetrahydrofolate--homocysteine transmethylase Methionine synthase Tetrahydrofolate methyltransferase Methionine synthase (cobalamin-dependent) N(5)-methyltetrahydrofolate methyltransferase 5-methyltetrahydrofolate--homocysteine S-methyltransferase N(5)-methyltetrahydrofolate--homocysteine cobalamin methyltransferase Tetrahydropteroylglutamate methyltransferase Vitamin B12 methyltransferase N-methyltetrahydrofolate:L-homocysteine methyltransferase Cobalamin-dependent methionine synthase Methionine synthetase Tetrahydropteroylglutamic methyltransferase N(5)-methyltetrahydrofolic--homocysteine vitamin B12 transmethylase B12 N(5)-methyltetrahydrofolate homocysteine methyltransferase In bacteria, the reducing agent is flavodoxin, and no further catalyst is needed (the flavodoxin is kept in the reduced state by NADPH and EC 1.18.1.2). For the mammalian enzyme, the reducing system involves NADPH and EC 1.16.1.8. Reactivation by reductive methylation is catalyzed by the enzyme itself, with S-adenosyl-L-methionine as the methyl donor and a reducing system. Zinc 5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine. The enzyme becomes inactivated occasionally during its cycle by oxidation of Co(I) to Co(II). Cobalamin http://purl.uniprot.org/mim/250940 Acts on the monoglutamate as well as the triglutamate folate, in contrast with EC 2.1.1.14, which acts only on the triglutamate. Precorrin-2 C20-methyltransferase S-adenosyl-L-methionine--precorrin-2 methyltransferase Precorrin-2 C(20)-methyltransferase S-adenosyl-L-methionine + precorrin-2 = S-adenosyl-L-homocysteine + precorrin-3A.