Reaction: cis-stilbene oxide + H2O = (+)-(1R,2R)-1,2-diphenylethane-1,2-diol
Other name(s): epoxide hydratase (ambiguous); microsomal epoxide hydratase; 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
Systematic name: cis-stilbene-oxide hydrolase
Comments: This is a key hepatic enzyme that is involved in the metabolism of numerous xenobiotics, such as 1,3-butadiene oxide, styrene oxide and the polycyclic aromatic hydrocarbon benzo[a]pyrene 4,5-oxide [5—7]. In a series of oxiranes with a lipophilic substituent of sufficient size (styrene oxides), monosubstituted as well as 1,1- and cis-1,2-disubstituted oxiranes serve as substrates or inhibitors of the enzyme. However, trans-1,2-disubstituted, tri-and tetra-substituted oxiranes are not substrates [9]. The reaction involves the formation of an hydroxyalkyl—enzyme intermediate [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, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. 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.
2. 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]
3. Oesch, F. Purification and specificity of a human microsomal epoxide hydratase. Biochem. J. 139 (1974) 77-88. [PMID: 4463951]
4. Oesch, F. and Daly, J. Solubilization, purification, and properties of a hepatic epoxide hydrase. Biochim. Biophys. Acta 227 (1971) 692-697.
5. 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]
6. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-333. [PMID: 15822179]
7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41-59. [PMID: 11154734]
8. 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]
9. Lacourciere, G.M. and Armstrong, R.N. Microsomal and soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes. Chem. Res. Toxicol. 7 (1994) 121-124. [PMID: 8199297]
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. [PMID: 15748653]