Biology:CYP7B1
 Generic protein structure example |
25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the CYP7B1 gene.[1][2][3] This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.
Function
This endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis.[3]
CYP7B was discovered by Stapleton[4] in a screen for transcripts expressed differentially in rat hippocampus versus the remainder of the brain. The encoded polypeptide, initially designated hct-1 (hippocampus transcript 1), had significant homology with CYP7A1.[4] The protein was designated CYP7B1 by the P450 Nomenclature Committee. Expression of the recombinant protein demonstrated 7alpha-hydroxylation activity for steroids (DHEA, pregnenolone) and oxysterols including 25-hydroxycholesterol and 27-hydroxycholesterol,[5][6][7] confirmed by knockout in mouse that abolished oxysterol hydroxylation in liver[8] and brain and steroid hydroxylation in multiple tissues.[9] Reporter tagging of the Cyp7b1 gene demonstrated that the enzyme is widely expressed, particularly strongly in brain, liver, kidney, heart, and spleen.[9]
References
- ↑ "Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease". J Clin Invest 102 (9): 1690–703. Dec 1998. doi:10.1172/JCI2962. PMID 9802883.
- ↑ "Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration". Am J Hum Genet 82 (2): 510–5. Feb 2008. doi:10.1016/j.ajhg.2007.10.001. PMID 18252231.
- ↑ 3.0 3.1 "Entrez Gene: CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9420.
- ↑ 4.0 4.1 "A novel cytochrome P450 expressed primarily in brain". J. Biol. Chem. 270 (50): 29739–45. December 1995. doi:10.1074/jbc.270.50.29739. PMID 8530364.
- ↑ "Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 4925–30. May 1997. doi:10.1073/pnas.94.10.4925. PMID 9144166. Bibcode: 1997PNAS...94.4925R.
- ↑ "Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA". J. Biol. Chem. 272 (38): 23995–4001. September 1997. doi:10.1074/jbc.272.38.23995. PMID 9295351.
- ↑ "7 alpha-hydroxylation of 27-hydroxycholesterol: biologic role in the regulation of cholesterol synthesis". J. Lipid Res. 38 (5): 1053–8. May 1997. doi:10.1016/S0022-2275(20)37229-1. PMID 9186922.
- ↑ "Disruption of the oxysterol 7alpha-hydroxylase gene in mice". J. Biol. Chem. 275 (22): 16536–42. June 2000. doi:10.1074/jbc.M001811200. PMID 10748048.
- ↑ 9.0 9.1 "Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation". J. Biol. Chem. 276 (26): 23937–44. June 2001. doi:10.1074/jbc.M011564200. PMID 11290741.
Further reading
- "Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis". Curr. Opin. Lipidol. 9 (2): 113–8. 1998. doi:10.1097/00041433-199804000-00006. PMID 9559267.
- "Dehydroepiandrosterone 7alpha-hydroxylation in human tissues: possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes". J. Steroid Biochem. Mol. Biol. 104 (3–5): 326–33. 2007. doi:10.1016/j.jsbmb.2007.03.026. PMID 17467270.
- "Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate cancer LNCaP cells". Biochem. Biophys. Res. Commun. 344 (2): 540–6. 2006. doi:10.1016/j.bbrc.2006.03.175. PMID 16630558. Bibcode: 2006BBRC..344..540T.
- "CYP7B expression and activity in fibroblast-like synoviocytes from patients with rheumatoid arthritis: regulation by proinflammatory cytokines". Arthritis Rheum. 52 (3): 770–8. 2005. doi:10.1002/art.20950. PMID 15751070.
- "The human cytochrome P4507B1: catalytic activity studies". J. Steroid Biochem. Mol. Biol. 92 (5): 383–9. 2005. doi:10.1016/j.jsbmb.2004.09.005. PMID 15698543.
- "CYP7B generates a selective estrogen receptor beta agonist in human prostate". J. Clin. Endocrinol. Metab. 89 (6): 2928–35. 2004. doi:10.1210/jc.2003-031847. PMID 15181079.
- "A functional C-G polymorphism in the CYP7B1 promoter region and its different distribution in Orientals and Caucasians". Pharmacogenomics J. 4 (4): 245–50. 2005. doi:10.1038/sj.tpj.6500236. PMID 15007371.
- "Transcriptional regulation of human oxysterol 7alpha-hydroxylase by sterol response element binding protein". Biochem. Biophys. Res. Commun. 316 (1): 158–64. 2004. doi:10.1016/j.bbrc.2004.02.029. PMID 15003524. Bibcode: 2004BBRC..316..158N.
- "Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease". Neuroscience 121 (2): 307–14. 2003. doi:10.1016/S0306-4522(03)00438-X. PMID 14521990.
- "Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population". J. Hum. Genet. 48 (5): 249–70. 2003. doi:10.1007/s10038-003-0021-7. PMID 12721789.
- "Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1". J. Lipid Res. 40 (12): 2195–203. 2000. doi:10.1016/S0022-2275(20)32094-0. PMID 10588945.
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