Cholesterol-5,6-oxide hydrolase explained

Cholesterol-5,6-oxide hydrolase
Ec Number:	3.3.2.11

Cholesterol-5,6-oxide hydrolase (cholesterol-epoxide hydrolase, ChEH) is an enzyme with systematic name 5,6alpha-epoxy-5alpha-cholestan-3beta-ol hydrolase.^{[1] [2] [3] [4] [5]} This enzyme catalyses the following chemical reaction

(1) 5,6alpha-epoxy-5alpha-cholestan-3beta-ol + H₂O

\rightleftharpoons 5alpha-cholestane-3beta,5alpha,6beta-triol

(2) 5,6beta-epoxy-5beta-cholestan-3beta-ol + H₂O

\rightleftharpoons 5alpha-cholestane-3beta,5alpha,6beta-triol

The enzyme works equally well with either epoxide as substrate on rat liver microsomes. The ChEH is an intracellular en membranous enzyme localized mainly on the endoplasmic reticulum of cells. Its molecular characterization revealed it is composed of two proteinaceous sub-units: the 3beta-hydroxysteroid delta8-delta7-isomerase (D8D7I), also known as the emopamil binding protein (EBP), which is the catalytic subunit, and the 3beta-hydroxysteroid delta7 reductase (DHCR7), which is the regulatory subunit.^[6] The ChEH is the "so called" microsomal antiestrogen binding site (AEBS), a secondary target of the antitumor drug tamoxifen and related compounds.^[7] The ChEH is inhibited by different pharmacological classes of drugs including anticancer drugs such as tamoxifen and natural substances such as ring B-oxysterols and poly-unsaturated fatty acids.^[8]

Notes and References

1. Levin W, Michaud DP, Thomas PE, Jerina DM . Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6 alpha-oxide and certain xenobiotic alkene and arene oxides . Archives of Biochemistry and Biophysics . 220 . 2 . 485–94 . February 1983 . 6401984 . 10.1016/0003-9861(83)90439-3 .
2. Oesch F, Timms CW, Walker CH, Guenthner TM, Sparrow A, Watabe T, Wolf CR . Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities . Carcinogenesis . 5 . 1 . 7–9 . January 1984 . 6690087 . 10.1093/carcin/5.1.7 .
3. Sevanian A, McLeod LL . Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase . The Journal of Biological Chemistry . 261 . 1 . 54–9 . January 1986 . 10.1016/S0021-9258(17)42429-X . 3941086 . free .
4. Fretland AJ, Omiecinski CJ . Epoxide hydrolases: biochemistry and molecular biology . Chemico-Biological Interactions . 129 . 1–2 . 41–59 . December 2000 . 11154734 . 10.1016/S0009-2797(00)00197-6 .
5. Newman JW, Morisseau C, Hammock BD . Epoxide hydrolases: their roles and interactions with lipid metabolism . Progress in Lipid Research . 44 . 1 . 1–51 . January 2005 . 15748653 . 10.1016/j.plipres.2004.10.001 .
6. de Medina P, Paillasse MR, Segala G, Poirot M, 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 U S A . 107 . 30 . 13520–5. August 2010 . 20615952 . 2922168 . 10.1073/pnas.1002922107. 2010PNAS..10713520D . free .
7. Kedjouar B, de Medina P, Oulad-Abdelghani M, Payré B, Silvente-Poirot S,Favre G, Faye JC, Poirot M . Molecular characterization of the microsomal tamoxifen binding site. J Biol Chem . 279 . 32 . 34048–61. June 2004. 15175332 . 10.1074/jbc.M405230200. free .
8. Silvente-Poirot S,Poirot M . Cholesterol epoxide hydrolase and cancer . Curr Opin Pharmacol . 12 . 6 . 696–703. August 2012 . 22917620. 10.1016/j.coph.2012.07.007.