Continued from EC 1.5
Sections
EC 1.6.1 With NAD+ or NADP+ as acceptor
EC 1.6.2 With a heme protein as acceptor
EC 1.6.3 With oxygen as acceptor
EC 1.6.4 With a disulfide as acceptor
EC 1.6.5 With a quinone or similar compound as acceptor
EC 1.6.6 With a nitrogenous group as acceptor
EC 1.6.8 With a flavin as acceptor
EC 1.6.99 With unknown physiological acceptors
Accepted name: NAD(P)+ transhydrogenase (Si-specific)
Reaction: NADPH + NAD+ = NADP+ + NADH
Other name(s): pyridine nucleotide transhydrogenase; transhydrogenase; NAD(P)+ transhydrogenase; nicotinamide adenine dinucleotide (phosphate) transhydrogenase; NAD+ transhydrogenase; NADH transhydrogenase; nicotinamide nucleotide transhydrogenase; NADPH-NAD+ transhydrogenase; pyridine nucleotide transferase; NADPH-NAD+ oxidoreductase; NADH-NADP+-transhydrogenase; NADPH:NAD+ transhydrogenase; H+-Thase; non-energy-linked transhydrogenase; NADPH:NAD+ oxidoreductase (B-specific); NAD(P)+ transhydrogenase (B-specific)
Systematic name: NADPH:NAD+ oxidoreductase (Si-specific)
Comments: The enzyme from Azotobacter vinelandii is a flavoprotein (FAD). It is Si-specific with respect to both NAD+ and NADP+.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9014-18-0
References:
1. Humphrey, G.F. The distribution and properties of transhydrogenase from animal tissues. Biochem. J. 65 (1957) 546-550. [PMID: 13412660]
2. You, K.-S. Stereospecificity for nicotinamide nucleotides in enzymatic and chemical hydride transfer reactions. CRC Crit. Rev. Biochem. 17 (1985) 313-451. [PMID: 3157549]
[EC 1.6.1.2 Transferred entry: NAD(P)+ transhydrogenase (Re/Si-specific). Now classified as EC 7.1.1.1, proton-translocating NAD(P)+ transhydrogenase (EC 1.6.1.2 created 1986, modified 2013, deleted 2023)]
Accepted name: NAD(P)+ transhydrogenase
Reaction: NADPH + NAD+ = NADP+ + NADH
Other name(s): pyridine nucleotide transhydrogenase; transhydrogenase (ambiguous); nicotinamide adenine dinucleotide (phosphate) transhydrogenase (ambiguous); NAD+ transhydrogenase (ambiguous); NADH transhydrogenase (misleading); nicotinamide nucleotide transhydrogenase (ambiguous); NADPH-NAD+ transhydrogenase (ambiguous); pyridine nucleotide transferase (ambiguous); NADPH-NAD+ oxidoreductase (ambiguous); NADH-NADP+-transhydrogenase (ambiguous); NADPH:NAD+ transhydrogenase; H+-Thase (ambiguous); non-energy-linked transhydrogenase (ambiguous)
Systematic name: NADPH:NAD+ oxidoreductase
Comments: The enzyme catalyses the NADPH-driven reduction of NAD+. This entry stands for enzymes whose stereo-specificity with respect to NADPH is not known. [cf. EC 1.6.1.1, NAD(P)+ transhydrogenase (Si-specific) and EC 1.6.1.2 NAD(P)+ transhydrogenase (Re/Si-specific)].
Links to other databases: BRENDA, EXPASY, GTD, KEGG Metacyc, CAS registry number:
References:
1. Keister D.L., San Pietro A., Stolzenbach F.E. Pyridine nucleotide transhydrogenase from spinach. I. Purification and properties. J. Biol. Chem. 235 (1960) 2989-2996. [PMID: 13752224]
Accepted name: NAD(P)+ transhydrogenase (ferredoxin)
Reaction: NADH + H+ + 2 NADP+ + 2 reduced ferredoxin [iron-sulfur] cluster = NAD+ + 2 NADPH + 2 oxidized ferredoxin [iron-sulfur] cluster
Other name(s): NADH-dependent reduced ferredoxin:NADP+ oxidoreductase; Nfn; nfnAB (gene names)
Systematic name: NADH:NADP+, ferredoxin oxidoreductase
Comments: The iron-sulfur flavoprotein complex, isolated from the bacterium Clostridium kluyveri, couples the exergonic reduction of NADP+ with reduced ferredoxin and the endergonic reduction of NADP+ with NADH.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Wang, S., Huang, H., Moll, J. and Thauer, R.K. NADP+ reduction with reduced ferredoxin and NADP+ reduction with NADH are coupled via an electron-bifurcating enzyme complex in Clostridium kluyveri. J. Bacteriol. 192 (2010) 5115-5123. [PMID: 20675474]
2. Demmer, J.K., Huang, H., Wang, S., Demmer, U., Thauer, R.K. and Ermler, U. Insights into flavin-based electron bifurcation via the NADH-dependent reduced ferredoxin:NADP oxidoreductase Structure. J. Biol. Chem. 290 (2015) 21985-21995. [PMID: 26139605]
3. Lubner, C.E., Jennings, D.P., Mulder, D.W., Schut, G.J., Zadvornyy, O.A., Hoben, J.P., Tokmina-Lukaszewska, M., Berry, L., Nguyen, D.M., Lipscomb, G.L., Bothner, B., Jones, A.K., Miller, A.F., King, P.W., Adams, M.WW. and Peters, J.W. Mechanistic insights into energy conservation by flavin-based electron bifurcation. Nat. Chem. Biol. 13 (2017) 655-659. [PMID: 28394885]
[EC 1.6.1.5 Transferred entry: proton-translocating NAD(P)+ transhydrogenase. Now EC 7.1.1.1, proton-translocating NAD(P)+ transhydrogenase (EC 1.6.1.5 created 2015, deleted 2018)]
Accepted name: cytochrome-b5 reductase
Reaction: NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5
Other name(s): cytochrome b5 reductase; dihydronicotinamide adenine dinucleotide-cytochrome b5 reductase; reduced nicotinamide adeninedinucleotide-cytochrome b5 reductase; NADH-ferricytochrome b5 oxidoreductase; NADH-cytochrome b5 reductase; NADH 5α-reductase ; NADH-cytochrome-b5 reductase
Systematic name: NADH:ferricytochrome-b5 oxidoreductase
Comments: A flavoprotein (FAD).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-25-1
References:
1. Mahler, H.R., Raw, I., Molinari, R. and do Amaral, D.F. Studies of electron transport enzymes. II. Isolation and some properties of a cytochrome-specific reduced diphosphopyridine nucleotide dehydrogenase from pig liver. J. Biol. Chem. 233 (1958) 230-239.
2. Strittmatter, P. Microsomal cytochrome b5 and cytochrome b5 reductase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds.), The Enzymes, 2nd ed., vol. 8, Academic Press, New York, 1963, p. 113-145.
3. Strittmatter, P. and Velick, S.F. The purification and properties of microsomal cytochrome reductase. J. Biol. Chem. 228 (1957) 785-799.
[EC 1.6.2.3 Deleted entry: cytochrome reductase (NADPH) (EC 1.6.2.3 created 1965, deleted 1972)]
Accepted name: NADPH—hemoprotein reductase
Reaction: NADPH + H+ + n oxidized hemoprotein = NADP+ + n reduced hemoprotein
Other name(s): CPR; FAD-cytochrome c reductase; NADP—cytochrome c reductase; NADP—cytochrome reductase; NADPH-dependent cytochrome c reductase; NADPH:P-450 reductase; NADPH:ferrihemoprotein oxidoreductase; NADPH—cytochrome P-450 oxidoreductase; NADPH—cytochrome c oxidoreductase; NADPH—cytochrome c reductase; NADPH—cytochrome p-450 reductase; NADPH—ferricytochrome c oxidoreductase; NADPH—ferrihemoprotein reductase; TPNH2 cytochrome c reductase; TPNH-cytochrome c reductase; aldehyde reductase (NADPH-dependent); cytochrome P-450 reductase; cytochrome c reductase (reduced nicotinamide adenine dinucleotide phosphate, NADPH, NADPH-dependent); dihydroxynicotinamide adenine dinucleotide phosphate-cytochrome c reductase; ferrihemoprotein P-450 reductase; reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase; reductase, cytochrome c (reduced nicotinamide adenine dinucleotide phosphate)
Systematic name: NADPH:hemoprotein oxidoreductase
Comments: A flavoprotein containing both FMN and FAD. This enzyme catalyses the transfer of electrons from NADPH, an obligatory two-electron donor, to microsomal P-450 monooxygenases (e.g. EC 1.14.14.1, unspecific monooxygenase) by stabilizing the one-electron reduced form of the flavin cofactors FAD and FMN. It also reduces cytochrome b5 and cytochrome c. 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.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-03-4
References:
1. Haas, E., Horecker, B.L. and Hogness, T.R. The enzymatic reduction of cytochrome c, cytochrome c reductase. J. Biol. Chem. 136 (1940) 747-774.
2. Horecker, B.L. Triphosphopyridine nucleotide-cytochrome c reductase in liver. J. Biol. Chem. 183, (1950) 593-605.
3. Lu, A.Y.H., Junk, K.W. and Coon, M.J. Resolution of the cytochrome P-450-containing ω-hydroxylation system of liver microsomes into three components. J. Biol. Chem. 244, (1969) 3714-3721. [PMID: 4389465]
4. Masters, B.S.S., Kamin, H., Gibson, Q.H. and Williams, C.H., Jr. Studies on the mechanism of microsomal triphosphopyridine nucleotide-cytochrome c reductase. J. Biol. Chem. 240, (1965) 921-931.
5. Williams, C.H.,Jr. and Kamin, H. Microsomal triphosphopyridine nucleotide-cytochrome c reductase in liver. J. Biol. Chem. 237, (1962) 587-595. p> 6.Masters, B.S.S., Bilimoria, M.H, Kamen, H. and Gibson, Q.H. The mechanism of 1- and 2-electron transfers catalyzed by reduced triphosphopyridine nucleotide-cytochrome c reductase. J. Biol. Chem. 240, (1965) 4081-4088. [PMID: 4378860]
7. Sevrioukova, I.F. and Peterson, J.A. NADPH-P-450 reductase: Structural and functional comparisons of the eukaryotic and prokaryotic isoforms. Biochimie 77, (1995) 562-572. [PMID: 8589067]
8. Wang, M., Roberts, D.L., Paschke, R., Shea, T.M., Masters, B.S.S. and Kim, J.-J.P. Three-dimensional structure of NADPH-cytochrome P450 reductase: Prototype for FMN- and FAD-containing enzymes. Proc. Natl. Acad. Sci. USA 94, (1997) 8411-8416. [PMID: 9237990]
9. Munro, A.W., Noble, M.A., Robledo, L., Daff, S.N. and Chapman, S.K. Determination of the redox properties of human NADPH-cytochrome P450 reductase. Biochemistry 40, (2001) 1956-1963. [PMID: 11329262]
10. Gutierrez, A., Grunau, A., Paine, M., Munro, A.W., Wolf, C.R., Roberts, G.C.K. and Scrutton, N.S. Electron transfer in human cytochrome P450 reductase. Biochem. Soc. Trans. 31, (2003) 497-501. [PMID: 12773143]
Accepted name: NADPH—cytochrome-c2 reductase
Reaction: NADPH + 2 ferricytochrome c2 = NADP+ + H+ + 2 ferrocytochrome c2
Other name(s): cytochrome c2 reductase (reduced nicotinamide adenine dinucleotide phosphate); cytochrome c2 reductase (reduced nicotinamide adinine dinucleotide phosphate, NADPH)
Systematic name: NADPH:ferricytochrome-c2 oxidoreductase
Comments: A flavoprotein (FAD).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-32-9
References:
1. Sabo, D.J. and Orlando, J.A. Isolation, purification, and some properties of reduced nicotinamide adenine dinucleotide phosphate-cytochrome c2 reductase from Rhodopseudomonas spheroides. J. Biol. Chem. 243 (1968) 3742-3749. [PMID: 4385431]
Accepted name: leghemoglobin reductase
Reaction: NAD(P)H + H+ + 2 ferrileghemoglobin = NAD(P)+ + 2 ferroleghemoglobin
Other name(s): ferric leghemoglobin reductase
Systematic name: NAD(P)H:ferrileghemoglobin oxidoreductase
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 60440-35-9
References:
1. Saari, L.L. and Klucas, R.V. Ferric leghemoglobin reductase from soybean root nodules. Arch. Biochem. Biophys. 231 (1984) 102-113. [PMID: 6539095]
Accepted name: NAD(P)H oxidase (H2O2-forming)
Reaction: NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
Other name(s): THOX2; ThOX; dual oxidase; p138tox; thyroid NADPH oxidase; thyroid oxidase; thyroid oxidase 2; NADPH oxidase; NAD(P)H:oxygen oxidoreductase; NAD(P)H oxidase
Systematic name: NAD(P)H:oxygen oxidoreductase (H2O2-forming)
Comments: Requires FAD, heme and calcium. When calcium is present, this transmembrane glycoprotein generates H2O2 by transfering electrons from intracellular NAD(P)H to extracellular molecular oxygen. The electron bridge within the enzyme contains one molecule of FAD and probably two heme groups. This flavoprotein is expressed at the apical membrane of thyrocytes, and provides H2O2 for the thyroid peroxidase-catalysed biosynthesis of thyroid hormones.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 77106-92-4
References:
1. Moreno, J.C., Bikker, H., Kempers, M.J., van Trotsenburg, A.S., Baas, F., de Vijlder, J.J., Vulsma, T. and Ris-Stalpers, C. Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N. Engl. J. Med. 347 (2002) 95-102. [PMID: 12110737]
2. De Deken, X., Wang, D., Dumont, J.E. and Miot, F. Characterization of ThOX proteins as components of the thyroid H2O2-generating system. Exp. Cell 273 (2002) 187-196. [PMID: 11822874]
3. De Deken, X., Wang, D., Many, M.C., Costagliola, S., Libert, F., Vassart, G., Dumont, J.E. and Miot, F. Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J. Biol. Chem. 275 (2000) 23227-23233. [PMID: 10806195]
4. Dupuy, C., Ohayon, R., Valent, A., Noel-Hudson, M.S., Deme, D. and Virion, A. Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs. J. Biol. Chem. 274 (1999) 37265-37269. [PMID: 10601291]
5. Leseney, A.M., Deme, D., Legue, O., Ohayon, R., Chanson, P., Sales, J.P., Pires de Carvalho, D., Dupuy, C. and Virion, A. Biochemical characterization of a Ca2+/NAD(P)H-dependent H2O2 generator in human thyroid tissue. Biochimie 81 (1999) 373-380. [PMID: 10401672]
6. Dupuy, C., Virion, A., Ohayon, R., Kaniewski, J., Deme, D. and Pommier, J. Mechanism of hydrogen peroxide formation catalyzed by NADPH oxidase in thyroid plasma membrane. J. Biol. Chem. 266 (1991) 3739-3743. [PMID: 1995628]
Accepted name: NAD(P)H oxidase (H2O-forming)
Reaction: 2 NAD(P)H + 2 H+ + O2 = 2 NAD(P)+ + 2 H2O
Systematic name: NAD(P)H:oxygen oxidoreductase (H2O-forming)
Comments: A flavoprotein (FAD). NADPH is a better substrate than NADH [1,3]. By removal of oxygen the enzyme is involved in aerobic tolerance in the thermophilic anaerobic archaeon Thermococcus profundus and in Giardia intestinalis, a microaerophilic single-celled parasite of the order Diplomonadida.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Brown, D.M., Upcroft, J.A. and Upcroft, P. A H2O-producing NADH oxidase from the protozoan parasite Giardia duodenalis. Eur. J. Biochem. 241 (1996) 155-161. [PMID: 8898901]
2. Li, L. and Wang, C.C. A likely molecular basis of the susceptibility of Giardia lamblia towards oxygen. Mol. Microbiol. 59 (2006) 202-211. [PMID: 16359329]
3. Jia, B., Park, S.C., Lee, S., Pham, B.P., Yu, R., Le, T.L., Han, S.W., Yang, J.K., Choi, M.S., Baumeister, W. and Cheong, G.W. Hexameric ring structure of a thermophilic archaeon NADH oxidase that produces predominantly H2O. FEBS J. 275 (2008) 5355-5366. [PMID: 18959761]
4. Jia, B., Lee, S., Pham, B.P., Cho, Y.S., Yang, J.K., Byeon, H.S., Kim, J.C. and Cheong, G.W. An archaeal NADH oxidase causes damage to both proteins and nucleic acids under oxidative stress. Mol. Cells 29 (2010) 363-371. [PMID: 20213313]
Accepted name: NADH oxidase (H2O2-forming)
Reaction: NADH + H+ + O2 = NAD+ + H2O2
Other name(s): NOX-1; H2O2-forming NADH oxidase
Systematic name: NADH:oxygen oxidoreductase (H2O2-forming)
Comments: A flavoprotein (FAD). The bacterium Streptococcus mutans contains two distinct NADH oxidases, a H2O2-forming enzyme and a H2O-forming enzyme (cf. EC 1.6.3.4, NADH oxidase (H2O-forming)) [1]. The enzymes from the anaerobic archaea Methanocaldococcus jannaschii [6] and Pyrococcus furiosus [3] also produce low amounts of H2O. Unlike EC 1.6.3.1 (NAD(P)H oxidase) it has no activity towards NADPH.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Higuchi, M., Shimada, M., Yamamoto, Y., Hayashi, T., Koga, T. and Kamio, Y. Identification of two distinct NADH oxidases corresponding to H2O2-forming oxidase and H2O-forming oxidase induced in Streptococcus mutans. J. Gen. Microbiol. 139 (1993) 2343-2351. [PMID: 8254304]
2. Ward, D.E., Donnelly, C.J., Mullendore, M.E., van der Oost, J., de Vos, W.M. and Crane, E.J., 3rd. The NADH oxidase from Pyrococcus furiosus. Implications for the protection of anaerobic hyperthermophiles against oxidative stress. Eur. J. Biochem. 268 (2001) 5816-5823. [PMID: 11722568]
3. Kengen, S.W., van der Oost, J. and de Vos, W.M. Molecular characterization of H2O2-forming NADH oxidases from Archaeoglobus fulgidus. Eur. J. Biochem. 270 (2003) 2885-2894. [PMID: 12823559]
4. Yang, X. and Ma, K. Characterization of an exceedingly active NADH oxidase from the anaerobic hyperthermophilic bacterium Thermotoga maritima. J. Bacteriol. 189 (2007) 3312-3317. [PMID: 17293421]
5. Hirano, J., Miyamoto, K. and Ohta, H. Purification and characterization of thermostable H2O2-forming NADH oxidase from 2-phenylethanol-assimilating Brevibacterium sp. KU1309. Appl. Microbiol. Biotechnol. 80 (2008) 71-78. [PMID: 18521590]
6. Case, C.L., Rodriguez, J.R. and Mukhopadhyay, B. Characterization of an NADH oxidase of the flavin-dependent disulfide reductase family from Methanocaldococcus jannaschii. Microbiology 155 (2009) 69-79. [PMID: 19118348]
Accepted name: NADH oxidase (H2O-forming)
Reaction: 2 NADH + 2 H+ + O2 = 2 NAD+ + 2 H2O
Other name(s): H2O-forming NADH oxidase; Nox-2
Systematic name: NADH:oxygen oxidoreductase (H2O-forming)
Comments: A flavoprotein (FAD). The bacterium Streptococcus mutans contains two distinct NADH oxidases, a H2O-forming enzyme and a H2O2-forming enzyme (cf. EC 1.6.3.3, NADH oxidase (H2O2-forming)) [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Schmidt, H.L., Stocklein, W., Danzer, J., Kirch, P. and Limbach, B. Isolation and properties of an H2O-forming NADH oxidase from Streptococcus faecalis. Eur. J. Biochem. 156 (1986) 149-155. [PMID: 3082630]
2. Higuchi, M., Shimada, M., Yamamoto, Y., Hayashi, T., Koga, T. and Kamio, Y. Identification of two distinct NADH oxidases corresponding to H2O2-forming oxidase and H2O-forming oxidase induced in Streptococcus mutans. J. Gen. Microbiol. 139 (1993) 2343-2351. [PMID: 8254304]
3. Matsumoto, J., Higuchi, M., Shimada, M., Yamamoto, Y. and Kamio, Y. Molecular cloning and sequence analysis of the gene encoding the H2O-forming NADH oxidase from Streptococcus mutans. Biosci. Biotechnol. Biochem. 60 (1996) 39-43. [PMID: 8824824]
4. Kawasaki, S., Ishikura, J., Chiba, D., Nishino, T. and Niimura, Y. Purification and characterization of an H2O-forming NADH oxidase from Clostridium aminovalericum: existence of an oxygen-detoxifying enzyme in an obligate anaerobic bacteria. Arch. Microbiol. 181 (2004) 324-330. [PMID: 15014929]
5. Zhang, Y.W., Tiwari, M.K., Gao, H., Dhiman, S.S., Jeya, M. and Lee, J.K. Cloning and characterization of a thermostable H2O-forming NADH oxidase from Lactobacillus rhamnosus. Enzyme Microb. Technol. 50 (2012) 255-262. [PMID: 22418266]
Accepted name: renalase
Reaction: (1) 1,2-dihydro-β-NAD(P) + H+ + O2 = β-NAD(P)+ + H2O2
(2) 1,6-dihydro-β-NAD(P) + H+ + O2 = β-NAD(P)+ + H2O2
Other name(s): αNAD(P)H oxidase/anomerase (incorrect); NAD(P)H:oxygen oxidoreductase (H2O2-forming, epimerising) (incorrect)
Systematic name: dihydro-NAD(P):oxygen oxidoreductase (H2O2-forming)
Comments: Requires FAD. Renalase, previously thought to be a hormone, is a flavoprotein secreted into the blood by the kidney that oxidizes the 1,2-dihydro- and 1,6-dihydro- isomeric forms of β-NAD(P)H back to β-NAD(P)+. These isomeric forms, generated by nonspecific reduction of β-NAD(P)+ or by tautomerization of β-NAD(P)H, are potent inhibitors of primary metabolism dehydrogenases and pose a threat to normal respiration.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Xu, J., Li, G., Wang, P., Velazquez, H., Yao, X., Li, Y., Wu, Y., Peixoto, A., Crowley, S. and Desir, G.V. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J. Clin. Invest. 115 (2005) 1275-1280. [PMID: 15841207]
2. Beaupre, B.A., Hoag, M.R., Roman, J., Forsterling, F.H. and Moran, G.R. Metabolic function for human renalase: oxidation of isomeric forms of β-NAD(P)H that are inhibitory to primary metabolism. Biochemistry 54 (2015) 795-806. [PMID: 25531177]
[EC 1.6.4.2 Transferred entry: now EC 1.8.1.7, glutathione-disulfide reductase (EC 1.6.4.2 created 1961, modified 1989, deleted 2002)]
[EC 1.6.4.3 Transferred entry: now EC 1.8.1.4 dihydrolipoamide dehydrogenase (EC 1.6.4.3 created 1961, modified 1976, deleted 1983)]
[EC 1.6.4.4 Transferred entry: now EC 1.8.1.8, protein-disulfide reductase (EC 1.6.4.4 created 1965, deleted 2002)]
[EC 1.6.4.5 Transferred entry: now EC 1.8.1.9, thioredoxin-disulfide reductase (EC 1.6.4.5 created 1972, deleted 2002)]
[EC 1.6.4.6 Transferred entry: now EC 1.8.1.10, CoA-glutathione reductase (EC 1.6.4.6 created 1972, deleted 2002)]
[EC 1.6.4.7 Transferred entry: now EC 1.8.1.11, asparagusate reductase (EC 1.6.4.7 created 1978, deleted 2002)]
[EC 1.6.4.8 Transferred entry: now EC 1.8.1.12, trypanothione-disulfide reductase (EC 1.6.4.8 created 1989, deleted 2002)]
[EC 1.6.4.9 Transferred entry: now EC 1.8.1.13, bis-γ-glutamylcystine reductase (EC 1.6.4.9 created 1992, deleted 2002)]
[EC 1.6.4.10 Transferred entry: now EC 1.8.1.14, CoA-disulfide reductase (EC 1.6.4.10 created 1992, deleted 2002)]
EC 1.6.5.8 transferred, now EC 7.2.1.1
EC 1.6.5.9 NADH:ubiquinone reductase (non-electrogenic)
EC 1.6.5.10 NADPH dehydrogenase (quinone)
EC 1.6.5.11 deleted, identical to EC 1.6.5.9
EC 1.6.5.12 demethylphylloquinone reductase
Accepted name: NAD(P)H dehydrogenase (quinone)
Reaction: NAD(P)H + H+ + a quinone = NAD(P)+ + a hydroquinone
For diagram of reaction click here.
Other name(s): menadione reductase; phylloquinone reductase; quinone reductase; dehydrogenase, reduced nicotinamide adenine dinucleotide (phosphate, quinone); DT-diaphorase; flavoprotein NAD(P)H-quinone reductase; menadione oxidoreductase; NAD(P)H dehydrogenase; NAD(P)H menadione reductase; NAD(P)H-quinone dehydrogenase; NAD(P)H-quinone oxidoreductase; NAD(P)H: (quinone-acceptor)oxidoreductase; NAD(P)H: menadione oxidoreductase; NADH-menadione reductase; naphthoquinone reductase; p-benzoquinone reductase; reduced NAD(P)H dehydrogenase; viologen accepting pyridine nucleotide oxidoreductase; vitamin K reductase; diaphorase; reduced nicotinamide-adenine dinucleotide (phosphate) dehydrogenase; vitamin-K reductase; NAD(P)H2 dehydrogenase (quinone); NQO1; QR1; NAD(P)H:(quinone-acceptor) oxidoreductase
Systematic name: NAD(P)H:quinone oxidoreductase
Comments: A flavoprotein. The enzyme catalyses a two-electron reduction and has a preference for short-chain acceptor quinones, such as ubiquinone, benzoquinone, juglone and duroquinone [6]. The animal, but not the plant, form of the enzyme is inhibited by dicoumarol.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-20-6
References:
1. di Prisco, G., Casola, L. and Giuditta, A. Purification and properties of a soluble reduced nicotinamide-adenine dinucleotide (phosphate) dehydrogenase from the hepatopancreas of Octopus vulgaris. Biochem. J. 105 (1967) 455-460. [PMID: 4171422]
2. Giuditta, A. and Strecker, H.J. Purification and some properties of a brain diaphorase. Biochim. Biophys. Acta 48 (1961) 10-19. [PMID: 13705804]
3. Märki, F. and Martius, C. Vitamin K-Reductase, Darsellung und Eigenschaften. Biochem. Z. 333 (1960) 111-135. [PMID: 13765127]
4. Misaka, E. and Nakanishi, K. Studies on menadione reductase of bakers' yeast. I. Purification, crystallization and some properties. J. Biochem. (Tokyo) 53 (1963) 465-471.
5. Wosilait, W.D. The reduction of vitamin K1 by an enzyme from dog liver. J. Biol. Chem. 235 (1960) 1196-1201. [PMID: 13846011]
6. Sparla, F., Tedeschi, G. and Trost, P. NAD(P)H:(quinone-acceptor) oxidoreductase of tobacco leaves is a flavin mononucleotide-containing flavoenzyme. Plant Physiol. 112 (1996) 249-258. [PMID: 12226388]
7. Braun, M., Bungert, S. and Friedrich, T. Characterization of the overproduced NADH dehydrogenase fragment of the NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli. Biochemistry 37 (1998) 1861-1867. [PMID: 9485311]
8. Jaiswal, A.K. Characterization and partial purification of microsomal NAD(P)H:quinone oxidoreductases. Arch. Biochem. Biophys. 375 (2000) 62-68. [PMID: 10683249]
9. Li, R., Bianchet, M.A., Talalay, P. and Amzel, L.M. The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction. Proc. Natl. Acad. Sci. USA 92 (1995) 8846-8850. [PMID: 7568029]
[EC 1.6.5.3 Transferred entry: NADH:ubiquinone reductase (H+-translocating). Now EC 7.1.1.2, NADH:ubiquinone reductase (H+-translocating) (EC 1.6.5.3 created 1961, deleted 1965, reinstated 1983, modified 2011, modified 2013, deleted 2018)]
Accepted name: monodehydroascorbate reductase (NADH)
Reaction: NADH + H+ + 2 monodehydroascorbate = NAD+ + 2 ascorbate
Other name(s): NADH:semidehydroascorbic acid oxidoreductase; MDHA; semidehydroascorbate reductase; AFR (ambiguous); AFR-reductase; ascorbic free radical reductase; ascorbate free radical reductase; SOR (ambiguous); MDAsA reductase (NADPH); SDA reductase; NADH:ascorbate radical oxidoreductase; NADH-semidehydroascorbate oxidoreductase; ascorbate free-radical reductase; NADH:AFR oxidoreductase; monodehydroascorbate reductase (NADH2)
Systematic name: NADH:monodehydroascorbate oxidoreductase
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9029-26-9
References:
1. Schulze, H.-U., Schott, H.-H. and Staudinger, H. Isolierung und Charakterisierung einer NADH: Semidehydroascorbinsäure-Oxidoreduktase aus Neurospora crassa. Hoppe-Seyler's Z. Physiol. Chem. 353 (1972) 1931-1942. [PMID: 4405497]
Accepted name: NADPH:quinone reductase
Reaction: NADPH + H+ + 2 quinone = NADP+ + 2 semiquinone
Other name(s): NADPH2:quinone reductase
Systematic name: NADPH:quinone oxidoreductase
Comments: A zinc enzyme, specific for NADPH. Catalyses the one-electron reduction of certain quinones, with the orthoquinones 1,2-naphthoquinone and 9,10-phenanthrenequinone being the best substrates [1]. Dicoumarol [cf. EC 1.6.5.2 NAD(P)H dehydrogenase (quinone)] and nitrofurantoin are competitive inhibitors with respect to the quinone substrate. The semiquinone free radical product may be non-enzymically reduced to the hydroquinone or oxidized back to quinone in the presence of O2 [1]. In some mammals the enzyme is abundant in the lens of the eye, where it is identified with the protein ζ-crystallin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9032-20-6
References:
1. Rao, P.V., Krishna, C.M. and Zigler, J.S., Jr. Identification and characterization of the enzymatic activity of ζ-crystallin from guinea pig lens. A novel NADPH:quinone oxidoreductase. J. Biol. Chem. 267 (1992) 96-102. [PMID: 1370456]
2. Duhaiman, A.S. Kinetic properties of camel lens ζ-crystallin. Int. J. Biochem. Cell Biol. 28 (1996) 1163-1168. [PMID: 8930141]
3. Bazzi, M.D. Interaction of camel lens ζ-crystallin with quinones: portrait of a substrate by fluorescence spectroscopy. Arch. Biochem. Biophys. 395 (2001) 185-190. [PMID: 11697855]
4. Tang, A. and Curthoys, N.P. Identification of ζ-crystallin/NADPH:quinone reductase as a renal glutaminase mRNA pH response element-binding protein. J. Biol. Chem. 276 (2001) 21375-21380. [PMID: 11294877]
Accepted name: p-benzoquinone reductase (NADPH)
Reaction: NADPH + H+ + p-benzoquinone = NADP+ + hydroquinone
For diagram of reaction click here.
Systematic name: NADPH:p-benzoquinone oxidoreductase
Comments: Involved in the 4-nitrophenol degradation pathway in bacteria.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Spain, J.C. and Gibson, D.T. Pathway for bioremediation of p-nitrophenol in a Moraxella sp. Appl. Environ. Microbiol. 57 (1991) 812-819.
Accepted name: 2-hydroxy-1,4-benzoquinone reductase
Reaction: 2-hydroxy-1,4-benzoquinone + NADH + H+ = hydroxyquinol + NAD+
For diagram of reaction click here.
Glossary: hydroxyquinol = 1,2,4-trihydroxybenzene
Other name(s): hydroxybenzoquinone reductase; 1,2,4-trihydroxybenzene:NAD oxidoreductase; NADH:2-hydroxy-1,4-benzoquinone oxidoreductase
Systematic name: NADH:2-hydroxy-1,4-benzoquinone oxidoreductase
Comments: A flavoprotein (FMN) that differs in substrate specificity from other quinone reductases. The enzyme in Burkholderia cepacia is inducible by 2,4,5-trichlorophenoxyacetate.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 214466-94-1
References:
1. Zaborina, O., Daubaras, D.L., Zago, A., Xun, L., Saido, K., Klem,T., Nikolic, D. and Chakrabarty, A.M. Novel pathway for conversion of chlorohydroxyquinol to maleylacetate in Burkholderia cepacia AC1100. J. Bacteriol. 180 (1998) 4667-4675. [PMID: 9721310]
[EC 1.6.5.8 Transferred entry: NADH:ubiquinone reductase (Na+-transporting). Now EC 7.2.1.1, NADH:ubiquinone reductase (Na+-transporting) (EC 1.6.5.8 created 2011, deleted 2018)]
Accepted name: NADH:quinone reductase (non-electrogenic)
Reaction: NADH + H+ + a quinone = NAD+ + a quinol
Other name(s): type II NAD(P)H:quinone oxidoreductase; NDE2 (gene name); ndh (gene name); NDH-II; NDH-2; NADH dehydrogenase (quinone) (ambiguous); ubiquinone reductase (ambiguous); coenzyme Q reductase (ambiguous); dihydronicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); DPNH-coenzyme Q reductase (ambiguous); DPNH-ubiquinone reductase (ambiguous); NADH-coenzyme Q oxidoreductase (ambiguous); NADH-coenzyme Q reductase (ambiguous); NADH-CoQ oxidoreductase (ambiguous); NADH-CoQ reductase (ambiguous); NADH-ubiquinone reductase (ambiguous); NADH-ubiquinone oxidoreductase (ambiguous); reduced nicotinamide adenine dinucleotide-coenzyme Q reductase (ambiguous); NADH-Q6 oxidoreductase (ambiguous); NADH2 dehydrogenase (ubiquinone) (ambiguous); NADH:ubiquinone oxidoreductase; NADH:ubiquinone reductase (non-electrogenic)
Systematic name: NADH:quinone oxidoreductase
Comments: A flavoprotein (FAD or FMN). Occurs in mitochondria of yeast and plants, and in aerobic bacteria. Has low activity with NADPH. Unlike EC 7.1.1.2, NADH:ubiquinone reductase (H+-translocating), this enzyme does not pump proteons of sodium ions across the membrane. It is also not sensitive to rotenone.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-04-0
References:
1. Bergsma, J., Strijker, R., Alkema, J.Y., Seijen, H.G. and Konings, W.N. NADH dehydrogenase and NADH oxidation in membrane vesicle from Bacillus subtilis. Eur. J. Biochem. 120 (1981) 599-606. [PMID: 6800784]
2. Møller, I.M, and Palmer, J.M. Direct evidence for the presence of a rotenone-resistant NADH dehydrogenase on the inner surface of plant mitochondria. Physiol. Plant. 54 (1982) 267-274.
3. de Vries, S. and Grivell, L.A. Purification and characterization of a rotenone-insensitive NADH:Q6 oxidoreductase from mitochondria of Saccharomyces cerevisiae. Eur. J. Biochem. 176 (1988) 377-384. [PMID: 3138118]
4. Kerscher, S.J., Okun, J.G. and Brandt, U. A single external enzyme confers alternative NADH:ubiquinone oxidoreductase activity in Yarrowia lipolytica. J. Cell Sci. 112 ( Pt 14) (1999) 2347-2354. [PMID: 10381390]
5. Rasmusson, A.G., Soole, K.L. and Elthon, T.E. Alternative NAD(P)H dehydrogenases of plant mitochondria. Annu. Rev. Plant Biol. 55 (2004) 23-39. [PMID: 15725055]
6. Melo, A.M., Bandeiras, T.M. and Teixeira, M. New insights into type II NAD(P)H:quinone oxidoreductases. Microbiol. Mol. Biol. Rev. 68 (2004) 603-616. [PMID: 15590775]
Accepted name: NADPH dehydrogenase (quinone)
Reaction: NADPH + H+ + a quinone = NADP+ + a quinol
Other name(s): reduced nicotinamide adenine dinucleotide phosphate (quinone) dehydrogenase; NADPH oxidase; NADPH2 dehydrogenase (quinone)
Systematic name: NADPH:(quinone-acceptor) oxidoreductase
Comments: A flavoprotein [1,2]. The enzyme from Escherichia coli is specific for NADPH and is most active with quinone derivatives and ferricyanide as electron acceptors [3]. Menaquinone can act as acceptor. The enzyme from hog liver is inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37256-37-4
References:
1. Koli, A.K., Yearby, C., Scott, W. and Donaldson, K.O. Purification and properties of three separate menadione reductases from hog liver. J. Biol. Chem. 244 (1969) 621-629. [PMID: 4388793]
2. Hayashi, M., Hasegawa, K., Oguni, Y. and Unemoto, T. Characterization of FMN-dependent NADH-quinone reductase induced by menadione in Escherichia coli. Biochim. Biophys. Acta 1035 (1990) 230-236. [PMID: 2118386]
3. Hayashi, M., Ohzeki, H., Shimada, H. and Unemoto, T. NADPH-specific quinone reductase is induced by 2-methylene-4-butyrolactone in Escherichia coli. Biochim. Biophys. Acta 1273 (1996) 165-170. [PMID: 8611590]
[EC 1.6.5.11 Deleted entry: NADH dehydrogenase (quinone). Identical to EC 1.6.5.9, NADH:quinone reductase (non-electrogenic) (EC 1.6.5.11 created 1972 as EC 1.6.99.5, transferred 2015 to EC 1.6.5.11, deleted 2019)]
Accepted name: demethylphylloquinone reductase
Reaction: demethylphylloquinone + NADPH + H+ = demethylphylloquinol + NADP+
Glossary: demethylphylloquinone = 2-phytyl-1,4-naphthoquinone
Other name(s): ndbB (gene name); NDC1 (gene name)
Systematic name: NADPH:demethylphylloquinone oxidoreductase
Comments: The enzyme, found in plants and cyanobacteria, is involved in the biosynthesis of phylloquinone (vitamin K1), an electron carrier associated with photosystem I. The enzyme is a type II NADPH dehydrogenase and requires a flavine adenine dinucleotide cofactor.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Fatihi, A., Latimer, S., Schmollinger, S., Block, A., Dussault, P.H., Vermaas, W.F., Merchant, S.S. and Basset, G.J. A dedicated type II NADPH dehydrogenase performs the penultimate step in the biosynthesis of vitamin K1 in Synechocystis and Arabidopsis. Plant Cell 27 (2015) 1730-1741. [PMID: 26023160]
[EC 1.6.6.2 Transferred entry: now EC 1.7.1.2, nitrate reductase [NAD(P)H] (EC 1.6.6.2 created 1961, deleted 2002)]
[EC 1.6.6.3 Transferred entry: now EC 1.7.1.3, nitrate reductase (NADPH) (EC 1.6.6.3 created 1961, deleted 2002)]
[EC 1.6.6.4 Transferred entry: now EC 1.7.1.4, nitrite reductase [NAD(P)H] (EC 1.6.6.4 created 1961, deleted 2002)]
[EC 1.6.6.5 Transferred entry: now EC 1.7.99.3 nitrite reductase (EC 1.6.6.5 created 1961, deleted 1964)]
[EC 1.6.6.6 Transferred entry: now EC 1.7.1.5, hyponitrite reductase (EC 1.6.6.6 created 1961, deleted 2002)]
[EC 1.6.6.7 Transferred entry: now EC 1.7.1.6, azobenzene reductase (EC 1.6.6.7 created 1961, deleted 2002)]
[EC 1.6.6.8 Transferred entry: now EC 1.7.1.7, GMP reductase (EC 1.6.6.8 created 1965, deleted 2002)]
[EC 1.6.6.9 Deleted entry: The activity is now known to be catalysed by EC 1.7.2.3, trimethylamine-N-oxide reductase. (EC 1.6.6.9 created 1972, deleted 2018)]
[EC 1.6.6.10 Transferred entry: now EC 1.7.1.9, nitroquinoline-N-oxide reductase (EC 1.6.6.10 created 1972, deleted 2002)]
[EC 1.6.6.11 Transferred entry: now EC 1.7.1.10, hydroxylamine reductase (NADH) (EC 1.6.6.11 created 1972, deleted 2002)]
[EC 1.6.6.12 Transferred entry: now EC 1.7.1.11, 4-(dimethylamino)phenylazoxybenzene reductase (EC 1.6.6.12 created 1989, deleted 2002)]
[EC 1.6.6.13 Transferred entry: now EC 1.7.1.12, N-hydroxy-2-acetamidofluorene reductase (EC 1.6.6.13 created 1989, deleted 2002)]
[EC 1.6.7.1 Transferred entry: now EC 1.18.1.2 ferredoxin-NADP+ reductase (EC 1.6.7.1 created 1972, deleted 1978)]
[EC 1.6.7.2 Transferred entry: now EC 1.18.1.1 rubredoxin-NAD+ reductase (EC 1.6.7.2 created 1972, deleted 1978)]
[EC 1.6.8.2 Transferred entry: now EC 1.5.1.30, flavin reductase (EC 1.6.8.2 created 1982, deleted 2002)]
Accepted name: NADPH dehydrogenase
Reaction: NADPH + H+ + acceptor = NADP+ + reduced acceptor
Other name(s): NADPH2 diaphorase; NADPH diaphorase; OYE; diaphorase; dihydronicotinamide adenine dinucleotide phosphate dehydrogenase; NADPH-dehydrogenase; NADPH-diaphorase; NADPH2-dehydrogenase; old yellow enzyme; reduced nicotinamide adenine dinucleotide phosphate dehydrogenase; TPNH dehydrogenase; TPNH-diaphorase; triphosphopyridine diaphorase; triphosphopyridine nucleotide diaphorase; NADPH2 dehydrogenase; NADPH:(acceptor) oxidoreductase
Systematic name: NADPH:acceptor oxidoreductase
Comments: A flavoprotein (FMN in yeast, FAD in plants).
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9001-68-7
References:
1. Åkesson, Å., Ehrenberg, A. and Theorell, H. Old yellow enzyme. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd ed., vol. 7, Academic Press, New York, 1963, p. 477-494.
2. Avron, M. and Jagendorf, A.T. Some further investigations on chloroplast TPNH diaphorase. Arch. Biochem. Biophys. 72 (1957) 17-24.
3. Jagendorf, A.T. Chloroplast TPNH diaphorase. Methods Enzymol. 6 (1963) 430-434.
4. Theorell, H. Das gelbe Oxydationsferment. Biochem. Z. 278 (1935) 263-290.
5. Theorell, H. and Åkesson, Å. Molecular weight and FMN content of crystalline "old yellow enzyme". Arch. Biochem. Biophys. 65 (1956) 439-448.
[EC 1.6.99.2 Transferred entry: now EC 1.6.5.2, NAD(P)H dehydrogenase (quinone). The enzyme was erroneously transferred from this sub-subclass in 1965 (EC 1.6.99.2 created 1961 as EC 1.6.5.2, transferred 1965 to EC 1.6.99.2, deleted 2005)]
[EC 1.6.99.3 covered by: NADH dehydrogenase. The activity is covered by EC 7.1.1.2, NADH:ubiquinone reductase (H+-translocating) (EC 1.6.99.3 created 1961 as EC 1.6.2.1, transferred 1965 to EC 1.6.99.3, modified 2018, deleted 2020)]
[EC 1.6.99.4 Transferred entry: now EC 1.18.1.2 ferredoxin-NADP+ reductase (EC 1.6.99.4 created 1965, deleted 1972)]
[EC 1.6.99.5 Transferred entry: NADH dehydrogenase (quinone). Transferred to EC 1.6.5.11, NADH dehydrogenase (quinone) (EC 1.6.99.5 created 1972, deleted 2014)]
[EC 1.6.99.6 Transferred entry: Transferred to EC 1.6.5.10, NADPH dehydrogenase (quinone) (EC 1.6.99.6 created 1972, deleted 2011)]
[EC 1.6.99.7 Transferred entry: now EC 1.5.1.34 6,7-dihydropteridine reductase. (EC 1.6.99.7 created 1972, modified 1981 (EC 1.6.99.10 created 1978, incorporated 1981), deleted 2003)]
[EC 1.6.99.8 Deleted entry: aquacobalamin reductase. This entry has been deleted since no specific enzyme catalysing this activity has been identified and it has been shown that aquacobalamin is efficiently reduced by free dihydroflavins and by non-specific reduced flavoproteins. (EC 1.6.99.8 created 1972, deleted 2002)]
[EC 1.6.99.9 Transferred entry: now EC 1.16.1.4, cob(II)alamin reductase (EC 1.6.99.9 created 1972, deleted 2002)]
EC 1.6.99.10 Deleted entry: now included with EC 1.5.1.34, 6,7-dihydropteridine reductase [EC 1.6.99.10 created 1978, deleted 1981]
[EC 1.6.99.11 Deleted entry: aquacobalamin reductase (NADPH). This entry has been deleted since the enzyme the entry was based on was later shown to be EC 1.2.1.51, pyruvate dehydrogenase (NADP+). On the other hand, it has been shown that non-enzymatic reduction of cob(III)alamin to cob(II)alamin occurs efficiently in the presence of free dihydroflavins or non-specific reduced flavoproteins. (EC 1.6.99.11 created 1989, deleted 2002)]
[EC 1.6.99.12 Transferred entry: now EC 1.16.1.6, cyanocobalamin reductase (cyanide-eliminating) (EC 1.6.99.12 created 1989, deleted 2002)]
[EC 1.6.99.13 Transferred entry: now EC 1.16.1.7, ferric-chelate reductase (EC 1.6.99.13 created 1992, deleted 2002)]