Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
(2) 5,6β-epoxy-5β-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
For diagram of reactions, click here
Glossary: cholesterol = cholest-5-en-3β-ol
Other name(s): cholesterol-epoxide hydrolase; ChEH
Systematic name: 5,6α-epoxy-5α-cholestan-3β-ol hydrolase
Comments: The activity has been attributed to the microsomal antiestrogen binding site, a complex formed by EC 5.3.3.5, cholestenol Δ-isomerase, and EC 1.3.1.21, 7-dehydrocholesterol reductase [6]. Both 5,6α-epoxy-5α-cholestan-3β-ol and 5,6β-epoxy-5β-cholestan-3β-ol are substrates [3]. The product is a competitive inhibitor of the reaction. 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) [3].
Links to other databases: BRENDA, EXPASY, G KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Levin, W., Michaud, D.P., Thomas, P.E. and Jerina, D.M. Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6 α-oxide and certain xenobiotic alkene and arene oxides. Arch. Biochem. Biophys. 220 (1983) 485-494. [PMID: 6401984]
2. Oesch, F., Timms, C.W., Walker, C.H., Guenthner, T.M., Sparrow, A., Watabe, T. and Wolf, C.R. Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5 (1984) 7-9. [PMID: 6690087]
3. Sevanian, A. and McLeod, L.L. Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase. J. Biol. Chem. 261 (1986) 54-59. [PMID: 3941086]
4. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41-59. [PMID: 11154734]
5. 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]
6. de Medina, P., Paillasse, M.R., Segala, G., Poirot, M. and Silvente-Poirot, S. Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands. Proc. Natl. Acad. Sci. USA 107 (2010) 13520-13525. [PMID: 20615952]