Reaction: (1) cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
(2) 1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine + H2O = 2-({[(4-methoxyphenyl)methyl](methyl)amino}methyl)-2-methylpropane-1,3-diol
Glossary: oxirane = ethylene oxide = a 3-membered oxygen-containing ring
oxetane = 1,3-propylene oxide = a 4-membered oxygen-containing ring
Other name(s): microsomal oxirane/oxetane hydrolase; epoxide hydratase (ambiguous); microsomal epoxide hydratase (ambiguous); epoxide hydrase; microsomal epoxide hydrase; arene-oxide hydratase (ambiguous); benzo[a]pyrene-4,5-oxide hydratase; benzo(a)pyrene-4,5-epoxide hydratase; aryl epoxide hydrase (ambiguous); cis-epoxide hydrolase; mEH; EPHX1 (gene name)
Systematic name: cis-stilbene-oxide hydrolase
Comments: This is a key hepatic enzyme that catalyses the hydrolytic ring opening of oxiranes (epoxides) and oxetanes to give the corresponding diols. The enzyme is involved in the metabolism of numerous substrates including the stereoselective hydrolytic ring opening of 7-oxabicyclo[4.1.0]hepta-2,4-dienes (arene oxides) to the corresponding trans-dihydrodiols. The reaction proceeds via a triad mechanism and involves the formation of an hydroxyalkyl-enzyme intermediate. Five epoxide-hydrolase enzymes have been identified in vertebrates 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).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Oesch, F. and Daly, J. Solubilization, purification, and properties of a hepatic epoxide hydrase. Biochim. Biophys. Acta 227 (1971) 692-697. [PMID: 4998715]
2. Jakoby, W.B. and Fjellstedt, T.A. Epoxidases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 7, Academic Press, New York, 1972, pp. 199-212.
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. [PMID: 4584115]
4. Oesch, F. Purification and specificity of a human microsomal epoxide hydratase. Biochem. J. 139 (1974) 77-88. [PMID: 4463951]
5. Lu, A.Y., Ryan, D., Jerina, D.M., Daly, J.W. and Levin, W. Liver microsomal expoxide hydrase. Solubilization, purification, and characterization. J. Biol. Chem. 250 (1975) 8283-8288. [PMID: 240858]
6. Bellucci, G., Chiappe, C. and Ingrosso, G. Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides. Chirality 6 (1994) 577-582. [PMID: 7986671]
7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41-59. [PMID: 11154734]
8. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-333. [PMID: 15822179]
9. 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. [PMID: 15748653]
10. Toselli, F., Fredenwall, M., Svensson, P., Li, X.Q., Johansson, A., Weidolf, L. and Hayes, M.A. Oxetane substrates of human microsomal epoxide hydrolase. Drug Metab. Dispos. 45 (2017) 966-973. [PMID: 28600384]