25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the CYP7B1gene. 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.
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.
CYP7B was discovered by Stapleton 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. 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- and 27-hydroxycholesterol, confirmed by knockout in mouse that abolished oxysterol hydroxylation in liver and brain and steroid hydroxylation in multiple tissues. Reporter tagging of the Cyp7b1 gene demonstrated that the enzyme is widely expressed, particularly strongly in brain, liver, liver, kidney, heart, and spleen.
^ abStapleton 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. PMID8530364. doi:10.1074/jbc.270.50.29739.
^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. PMID9295351. doi:10.1074/jbc.272.38.23995.
^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. PMID9186922.
^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. PMID10748048. doi:10.1074/jbc.M001811200.
^ abRose 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. PMID11290741. doi:10.1074/jbc.M011564200.
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. PMID17467270. doi:10.1016/j.jsbmb.2007.03.026.
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. PMID16630558. doi:10.1016/j.bbrc.2006.03.175.
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. PMID15751070. doi:10.1002/art.20950.
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. PMID15181079. doi:10.1210/jc.2003-031847.
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. PMID15007371. doi:10.1038/sj.tpj.6500236.
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. PMID15003524. doi:10.1016/j.bbrc.2004.02.029.
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. PMID14521990. doi:10.1016/S0306-4522(03)00438-X.
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. PMID12721789. doi:10.1007/s10038-003-0021-7.
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. PMID10588945.