Biology:Cholesterol-5,6-oxide hydrolase
| Cholesterol-5,6-oxide hydrolase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 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 | ||||||||
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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 [math]\displaystyle{ \rightleftharpoons }[/math] 5alpha-cholestane-3beta,5alpha,6beta-triol
- (2) 5,6beta-epoxy-5beta-cholestan-3beta-ol + H2O [math]\displaystyle{ \rightleftharpoons }[/math] 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]
References
- ↑ "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. doi:10.1016/0003-9861(83)90439-3. PMID 6401984.
- ↑ "Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities". Carcinogenesis 5 (1): 7–9. January 1984. doi:10.1093/carcin/5.1.7. PMID 6690087.
- ↑ "Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase". The Journal of Biological Chemistry 261 (1): 54–9. January 1986. doi:10.1016/S0021-9258(17)42429-X. PMID 3941086.
- ↑ "Epoxide hydrolases: biochemistry and molecular biology". Chemico-Biological Interactions 129 (1–2): 41–59. December 2000. doi:10.1016/S0009-2797(00)00197-6. PMID 11154734.
- ↑ "Epoxide hydrolases: their roles and interactions with lipid metabolism". Progress in Lipid Research 44 (1): 1–51. January 2005. doi:10.1016/j.plipres.2004.10.001. PMID 15748653.
- ↑ "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. doi:10.1073/pnas.1002922107. PMID 20615952. Bibcode: 2010PNAS..10713520D.
- ↑ "Molecular characterization of the microsomal tamoxifen binding site". J Biol Chem 279 (32): 34048–61. June 2004. doi:10.1074/jbc.M405230200. PMID 15175332.
- ↑ "Cholesterol epoxide hydrolase and cancer". Curr Opin Pharmacol 12 (6): 696–703. August 2012. doi:10.1016/j.coph.2012.07.007. PMID 22917620.
External links
- +cholesterol-5,6-oxide+hydrolase at the US National Library of Medicine Medical Subject Headings (MeSH)
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