CYP7B1
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.[5][6][7] 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
[edit]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.[7]
CYP7B was discovered by Stapleton[8] 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.[8] 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,[9][10][11] confirmed by knockout in mouse that abolished oxysterol hydroxylation in liver[12] and brain and steroid hydroxylation in multiple tissues.[13] Reporter tagging of the Cyp7b1 gene demonstrated that the enzyme is widely expressed, particularly strongly in brain, liver, kidney, heart, and spleen.[13]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000172817 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039519 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW (Dec 1998). "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. doi:10.1172/JCI2962. PMC 509117. PMID 9802883.
- ^ Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH (Feb 2008). "Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration". Am J Hum Genet. 82 (2): 510–5. doi:10.1016/j.ajhg.2007.10.001. PMC 2426914. PMID 18252231.
- ^ a b "Entrez Gene: CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1".
- ^ a b Stapleton G, Steel M, Richardson M, Mason JO, Rose KA, Morris RG, Lathe R (December 1995). "A novel cytochrome P450 expressed primarily in brain". J. Biol. Chem. 270 (50): 29739–45. doi:10.1074/jbc.270.50.29739. PMID 8530364.
- ^ Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Björkhem I, Seckl J, Lathe R (May 1997). "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. Bibcode:1997PNAS...94.4925R. doi:10.1073/pnas.94.10.4925. PMC 24607. PMID 9144166.
- ^ Schwarz M, Lund EG, Lathe R, Björkhem I, Russell DW (September 1997). "Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA". J. Biol. Chem. 272 (38): 23995–4001. doi:10.1074/jbc.272.38.23995. PMID 9295351.
- ^ Martin KO, Reiss AB, Lathe R, Javitt NB (May 1997). "7 alpha-hydroxylation of 27-hydroxycholesterol: biologic role in the regulation of cholesterol synthesis". J. Lipid Res. 38 (5): 1053–8. doi:10.1016/S0022-2275(20)37229-1. PMID 9186922.
- ^ Li-Hawkins J, Lund EG, Turley SD, Russell DW (June 2000). "Disruption of the oxysterol 7alpha-hydroxylase gene in mice". J. Biol. Chem. 275 (22): 16536–42. doi:10.1074/jbc.M001811200. PMID 10748048.
- ^ a b Rose K, Allan A, Gauldie S, Stapleton G, Dobbie L, Dott K, Martin C, Wang L, Hedlund E, Seckl JR, Gustafsson JA, Lathe R (June 2001). "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. doi:10.1074/jbc.M011564200. PMID 11290741.
Further reading
[edit]- Schwarz M, Lund EG, Russell DW (1998). "Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis". Curr. Opin. Lipidol. 9 (2): 113–8. doi:10.1097/00041433-199804000-00006. PMID 9559267.
- Hennebert O, Chalbot S, Alran S, Morfin R (2007). "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. doi:10.1016/j.jsbmb.2007.03.026. PMID 17467270. S2CID 53295289.
- Tang W, Norlin M (2006). "Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate cancer LNCaP cells". Biochem. Biophys. Res. Commun. 344 (2): 540–6. doi:10.1016/j.bbrc.2006.03.175. PMID 16630558.
- Dulos J, van der Vleuten MA, Kavelaars A, Heijnen CJ, Boots AM (2005). "CYP7B expression and activity in fibroblast-like synoviocytes from patients with rheumatoid arthritis: regulation by proinflammatory cytokines". Arthritis Rheum. 52 (3): 770–8. doi:10.1002/art.20950. PMID 15751070.
- Kim SB, Chalbot S, Pompon D, Jo DH, Morfin R (2005). "The human cytochrome P4507B1: catalytic activity studies". J. Steroid Biochem. Mol. Biol. 92 (5): 383–9. doi:10.1016/j.jsbmb.2004.09.005. PMID 15698543. S2CID 25621636.
- Martin C, Ross M, Chapman KE, Andrew R, Bollina P, Seckl JR, Habib FK (2004). "CYP7B generates a selective estrogen receptor beta agonist in human prostate". J. Clin. Endocrinol. Metab. 89 (6): 2928–35. doi:10.1210/jc.2003-031847. PMID 15181079.
- Jakobsson J, Karypidis H, Johansson JE, Roh HK, Rane A, Ekström L (2005). "A functional C-G polymorphism in the CYP7B1 promoter region and its different distribution in Orientals and Caucasians". Pharmacogenomics J. 4 (4): 245–50. doi:10.1038/sj.tpj.6500236. PMID 15007371. S2CID 25094661.
- Norlin M, Chiang JY (2004). "Transcriptional regulation of human oxysterol 7alpha-hydroxylase by sterol response element binding protein". Biochem. Biophys. Res. Commun. 316 (1): 158–64. doi:10.1016/j.bbrc.2004.02.029. PMID 15003524.
- Yau JL, Rasmuson S, Andrew R, Graham M, Noble J, Olsson T, Fuchs E, Lathe R, Seckl JR (2003). "Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease". Neuroscience. 121 (2): 307–14. doi:10.1016/S0306-4522(03)00438-X. PMID 14521990. S2CID 46593148.
- Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y (2003). "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. doi:10.1007/s10038-003-0021-7. PMID 12721789.
- Wu Z, Martin KO, Javitt NB, Chiang JY (2000). "Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1". J. Lipid Res. 40 (12): 2195–203. doi:10.1016/S0022-2275(20)32094-0. PMID 10588945.
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