EC 3.3.2.10 - Soluble epoxide hydrolase
IntEnz Enzyme Nomenclature
EC 3.3.2.10
Names
epoxide hydratase [ambiguous]
arene-oxide hydratase [ambiguous]
aryl epoxide hydrase [ambiguous]
trans-stilbene oxide hydrolase
sEH
cytosolic epoxide hydrolase
Reaction
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19037 [IUBMB]an epoxideName origin: UniProt - CHECKED (C)Formula: C2OR4
Charge: 0ChEBI compound status: CHECKED (C)H2OName origin: UniProt - CHECKED (C)Formula: H2O
Charge: 0ChEBI compound status: CHECKED (C)=
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 (epoxyeicosatrienoic 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-eicosatetraenoic 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
References
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The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.Proc. Natl. Acad. Sci. USA 100 : 1558-1563 (2003). [PMID: 12574510]
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The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.Proc. Natl. Acad. Sci. USA 100 : 1552-1557 (2003). [PMID: 12574508]
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Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.Xenobiotica 3 : 305-340 (1973). [PMID: 4584115]
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Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.Annu. Rev. Pharmacol. Toxicol. 45 : 311-333 (2005). [PMID: 15822179]
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Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.Circ. Res. 87 : 992-998 (2000). [PMID: 11090543]
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The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate.J. Am. Chem. Soc. 115 : 10466-10456 (1993).
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Epoxide hydrolases: biochemistry and molecular biology.Chem. Biol. Interact. 129 : 41-59 (2000). [PMID: 11154734]
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Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis.Arch. Biochem. Biophys. 316 : 443-451 (1995). [PMID: 7840649]
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Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase.J. Biol. Chem. 261 : 6332-6337 (1986). [PMID: 3009453]
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Epoxide hydrolases: their roles and interactions with lipid metabolism.Prog. Lipid Res. 44 : 1-51 (2005). [PMID: 15748653]
[EC 3.3.2.10 created 2006 (EC 3.3.2.3 part-incorporated 2006)]