| Cholesterol-5,6-oxide hydrolase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.3.2.11 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Cholesterol-5,6-oxide hydrolase (EC 3.3.2.11, 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 5alpha-cholestane-3beta,5alpha,6beta-triol
- (2) 5,6beta-epoxy-5beta-cholestan-3beta-ol + H2O 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]
- ^ Levin W, Michaud DP, Thomas PE, Jerina DM (February 1983). "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. doi:10.1016/0003-9861(83)90439-3. PMID 6401984.
- ^ Oesch F, Timms CW, Walker CH, Guenthner TM, Sparrow A, Watabe T, Wolf CR (January 1984). "Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities". Carcinogenesis. 5 (1): 7–9. doi:10.1093/carcin/5.1.7. PMID 6690087.
- ^ Sevanian A, McLeod LL (January 1986). "Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase". The Journal of Biological Chemistry. 261 (1): 54–9. doi:10.1016/S0021-9258(17)42429-X. PMID 3941086.
- ^ Fretland AJ, Omiecinski CJ (December 2000). "Epoxide hydrolases: biochemistry and molecular biology". Chemico-Biological Interactions. 129 (1–2): 41–59. doi:10.1016/S0009-2797(00)00197-6. PMID 11154734.
- ^ Newman JW, Morisseau C, Hammock BD (January 2005). "Epoxide hydrolases: their roles and interactions with lipid metabolism". Progress in Lipid Research. 44 (1): 1–51. doi:10.1016/j.plipres.2004.10.001. PMID 15748653.
- ^ de Medina P, Paillasse MR, Segala G, Poirot M, Silvente-Poirot S (August 2010). "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. Bibcode:2010PNAS..10713520D. doi:10.1073/pnas.1002922107. PMC 2922168. PMID 20615952.
- ^ Kedjouar B, de Medina P, Oulad-Abdelghani M, Payré B, Silvente-Poirot S, Favre G, Faye JC, Poirot M (June 2004). "Molecular characterization of the microsomal tamoxifen binding site". J Biol Chem. 279 (32): 34048–61. doi:10.1074/jbc.M405230200. PMID 15175332.
- ^ Silvente-Poirot S, Poirot M (August 2012). "Cholesterol epoxide hydrolase and cancer". Curr Opin Pharmacol. 12 (6): 696–703. doi:10.1016/j.coph.2012.07.007. PMID 22917620.