EC |
1.3.1.74 |
Accepted name: |
2-alkenal reductase [NAD(P)+] |
Reaction: |
a n-alkanal + NAD(P)+ = an alk-2-enal + NAD(P)H + H+ |
Other name(s): |
NAD(P)H-dependent alkenal/one oxidoreductase; NADPH:2-alkenal α,β-hydrogenase; 2-alkenal reductase |
Systematic name: |
n-alkanal:NAD(P)+ 2-oxidoreductase |
Comments: |
Highly specific for 4-hydroxynon-2-enal and non-2-enal. Alk-2-enals of shorter chain have lower affinities. Exhibits high activities also for alk-2-enones such as but-3-en-2-one and pent-3-en-2-one. Inactive with cyclohex-2-en-1-one and 12-oxophytodienoic acid. Involved in the detoxication of α,β-unsaturated aldehydes and ketones [cf. EC 1.3.1.102, 2-alkenal reductase (NADP+)]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 52227-95-9 |
References: |
1. |
Mano, J., Torii, Y., Hayashi, S., Takimoto, K., Matsui, K., Nakamura, K., Inzé, D., Babiychuk, E., Kushnir, S. and Asada, K. The NADPH:quinone oxidoreductase P1-ζ-crystallin in Arabidopsis catalyzes the α,β-hydrogenation of 2-alkenals: detoxication of the lipid peroxide-derived reactive aldehydes. Plant Cell Physiol. 43 (2002) 1445–1455. [PMID: 12514241] |
2. |
Dick, R.A., Kwak, M.K., Sutter, T.R. and Kensler, T.W. Antioxidative function and substrate specificity of NAD(P)H-dependent alkenal/one oxidoreductase. A new role for leukotriene B4 12-hydroxydehydrogenase/15-oxoprostaglandin 13-reductase. J. Biol. Chem. 276 (2001) 40803–40810. [DOI] [PMID: 11524419] |
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[EC 1.3.1.74 created 2003, modified 2014] |
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EC
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1.14.13.30
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Transferred entry: | leukotriene-B4 20-monooxygenase. Now EC 1.14.14.94, leukotriene-B4 20-monooxygenase
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[EC 1.14.13.30 created 1989, deleted 2018] |
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EC
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1.14.13.194
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Transferred entry: | phylloquinone ω-hydroxylase. Now EC 1.14.14.78, phylloquinone ω-hydroxylase
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[EC 1.14.13.194 created 2014, deleted 2018] |
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EC |
1.14.14.78 |
Accepted name: |
phylloquinone ω-hydroxylase |
Reaction: |
phylloquinone + [reduced NADPH—hemoprotein reductase] + O2 = ω-hydroxyphylloquinone + [oxidized NADPH—hemoprotein reductase] + H2O |
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For diagram of vitamin K biosynthesis, click here |
Other name(s): |
vitamin K1 ω-hydroxylase; CYP4F2; CYP4F11 |
Systematic name: |
phylloquinone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxyphylloquinone-forming) |
Comments: |
A cytochrome P-450 (heme-thiolate) protein. Isolated from human tissue. The enzyme will also act on menaquinone-4. Prolonged action of CYP4F2, but not CYP4F11, on the ω hydroxyl group oxidizes it to the corresponding carboxylic acid. CYP4F2 also oxidizes leukotriene B4; see EC 1.14.13.30, leukotriene-B4 20-monooxygenase [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Jin, R., Koop, D.R., Raucy, J.L. and Lasker, J.M. Role of human CYP4F2 in hepatic catabolism of the proinflammatory agent leukotriene B4. Arch. Biochem. Biophys. 359 (1998) 89–98. [DOI] [PMID: 9799565] |
2. |
Tang, Z., Salamanca-Pinzon, S.G., Wu, Z.L., Xiao, Y. and Guengerich, F.P. Human cytochrome P450 4F11: heterologous expression in bacteria, purification, and characterization of catalytic function. Arch. Biochem. Biophys. 494 (2010) 86–93. [DOI] [PMID: 19932081] |
3. |
Edson, K.Z., Prasad, B., Unadkat, J.D., Suhara, Y., Okano, T., Guengerich, F.P. and Rettie, A.E. Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. Biochemistry 52 (2013) 8276–8285. [DOI] [PMID: 24138531] |
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[EC 1.14.14.78 created 2014 as EC 1.14.13.194, transferred 2018 to EC 1.14.14.78] |
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EC |
1.14.14.94 |
Accepted name: |
leukotriene-B4 20-monooxygenase |
Reaction: |
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate + [reduced NADPH—hemoprotein reductase] + O2 = (6Z,8E,10E,14Z)-(5S,12R)-5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + [oxidized NADPH—hemoprotein reductase] + H2O |
Other name(s): |
leukotriene-B4 20-hydroxylase; leucotriene-B4 ω-hydroxylase; LTB4 20-hydroxylase; LTB4 ω-hydroxylase; CYP4F2 (gene name); CYP4F3 (gene name) |
Systematic name: |
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (20-hydroxylating) |
Comments: |
A cytochrome P-450 (heme-thiolate) protein found in mammals. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 90119-11-2 |
References: |
1. |
Romano, M.C., Eckardt, R.D., Bender, P.E., Leonard, T.B., Straub, K.M. and Newton, J.F. Biochemical characterization of hepatic microsomal leukotriene B4 hydroxylases. J. Biol. Chem. 262 (1987) 1590–1595. [PMID: 3027095] |
2. |
Shak, S. and Goldstein, I.M. Leukotriene B4 ω-hydroxylase in human polymorphonuclear leukocytes. Partial purification and identification as a cytochrome P-450. J. Clin. Invest. 76 (1985) 1218–1228. [DOI] [PMID: 4044832] |
3. |
Soberman, R.J., Harper, T.W., Murphy, R.C. and Austen, K.F. Identification and functional characterization of leukotriene B4 20-hydroxylase of human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. USA 82 (1985) 2292–2295. [DOI] [PMID: 2986111] |
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[EC 1.14.14.94 created 1989 as EC 1.14.13.30, transferred 2018 to EC 1.14.14.94] |
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EC |
3.3.2.6 |
Accepted name: |
leukotriene-A4 hydrolase |
Reaction: |
leukotriene A4 + H2O = leukotriene B4 |
Glossary: |
leukotriene A4 = (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate
leukotriene B4 = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate |
Other name(s): |
LTA4 hydrolase; LTA4H; leukotriene A4 hydrolase |
Systematic name: |
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase |
Comments: |
This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates [6] (see EC 3.4.11.6, aminopeptidase B). It also converts leukotriene A4 into leukotriene B4, unlike EC 3.3.2.10, soluble epoxide hydrolase, which converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) [5]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 90119-07-6 |
References: |
1. |
Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils. Biochim. Biophys. Acta 840 (1985) 43–50. [DOI] [PMID: 3995081] |
2. |
Minami, M., Ohno, S., Kawasaki, H., Rådmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T., Seyama, Y. and Suzuki, K. Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase - complete primary structure of an enzyme involved in eicosanoid synthesis. J. Biol. Chem. 262 (1987) 13873–13876. [PMID: 3654641] |
3. |
Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453] |
4. |
Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653] |
5. |
Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734] |
6. |
Orning, L., Gierse, J.K. and Fitzpatrick, F.A. The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity. J. Biol. Chem. 269 (1994) 11269. [PMID: 8157657] |
7. |
Ohishi, N., Izumi, T., Minami, M., Kitamura, S., Seyama, Y., Ohkawa, S., Terao, S., Yotsumoto, H., Takaku, F. and Shimizu, T. Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers. J. Biol. Chem. 262 (1987) 10200–10205. [PMID: 3038871] |
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[EC 3.3.2.6 created 1989, modified 2006] |
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EC |
3.3.2.10 |
Accepted name: |
soluble epoxide hydrolase |
Reaction: |
an epoxide + H2O = a glycol |
Other name(s): |
epoxide hydrase (ambiguous); epoxide hydratase (ambiguous); arene-oxide hydratase (ambiguous); aryl epoxide hydrase (ambiguous); trans-stilbene oxide hydrolase; sEH; cytosolic epoxide hydrolase |
Systematic name: |
epoxide hydrolase |
Comments: |
Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl—enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [7]. |
Links to other databases: |
BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9048-63-9 |
References: |
1. |
Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme
with novel lipid phosphate phosphatase activity. Proc. Natl. Acad. Sci. USA 100 (2003) 1558–1563. [DOI] [PMID: 12574510] |
2. |
Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc. Natl. Acad. Sci. USA 100 (2003) 1552–1557. [DOI] [PMID: 12574508] |
3. |
Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305–340. [DOI] [PMID: 4584115] |
4. |
Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311–333. [DOI] [PMID: 15822179] |
5. |
Yu, Z., Xu, F., Huse, L.M., Morisseau, C., Draper, A.J., Newman, J.W., Parker, C., Graham, L., Engler, M.M., Hammock, B.D., Zeldin, D.C. and Kroetz, D.L. Soluble epoxide hydrolase regulates hydrolysis of vasoactive
epoxyeicosatrienoic acids. Circ. Res. 87 (2000) 992–998. [PMID: 11090543] |
6. |
Lacourciere, G.M. and Armstrong, R.N. The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate. J. Am. Chem. Soc. 115 (1993) 10466. |
7. |
Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [DOI] [PMID: 11154734] |
8. |
Zeldin, D.C., Wei, S., Falck, J.R., Hammock, B.D., Snapper, J.R. and Capdevila, J.H. Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase:
substrate structural determinants of asymmetric catalysis. Arch. Biochem. Biophys. 316 (1995) 443–451. [DOI] [PMID: 7840649] |
9. |
Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453] |
10. |
Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [DOI] [PMID: 15748653] |
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[EC 3.3.2.10 created 2006 (EC 3.3.2.3 created 1978, part incorporated 2006)] |
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