CYP7B1 explained

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.

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.^[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. Reporter tagging of the Cyp7b1 gene demonstrated that the enzyme is widely expressed, particularly strongly in brain, liver, kidney, heart, and spleen.^[9]

Further reading

• Schwarz M, Lund EG, Russell DW . Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis . Curr. Opin. Lipidol. . 9 . 2 . 113–8 . 1998 . 9559267 . 10.1097/00041433-199804000-00006 .
• Hennebert O, Chalbot S, Alran S, Morfin R . 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 . 17467270 . 10.1016/j.jsbmb.2007.03.026 . 53295289 .
• Tang W, Norlin M . Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate cancer LNCaP cells . Biochem. Biophys. Res. Commun. . 344 . 2 . 540–6 . 2006 . 16630558 . 10.1016/j.bbrc.2006.03.175 .
• Dulos J, van der Vleuten MA, Kavelaars A, Heijnen CJ, Boots AM . CYP7B expression and activity in fibroblast-like synoviocytes from patients with rheumatoid arthritis: regulation by proinflammatory cytokines . Arthritis Rheum. . 52 . 3 . 770–8 . 2005 . 15751070 . 10.1002/art.20950 . free .
• Kim SB, Chalbot S, Pompon D, Jo DH, Morfin R . The human cytochrome P4507B1: catalytic activity studies . J. Steroid Biochem. Mol. Biol. . 92 . 5 . 383–9 . 2005 . 15698543 . 10.1016/j.jsbmb.2004.09.005 . 25621636 .
• Martin C, Ross M, Chapman KE, Andrew R, Bollina P, Seckl JR, Habib FK . CYP7B generates a selective estrogen receptor beta agonist in human prostate . J. Clin. Endocrinol. Metab. . 89 . 6 . 2928–35 . 2004 . 15181079 . 10.1210/jc.2003-031847 . free .
• Jakobsson J, Karypidis H, Johansson JE, Roh HK, Rane A, Ekström L . 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 . 15007371 . 10.1038/sj.tpj.6500236 . 25094661 .
• Norlin M, Chiang JY . Transcriptional regulation of human oxysterol 7alpha-hydroxylase by sterol response element binding protein . Biochem. Biophys. Res. Commun. . 316 . 1 . 158–64 . 2004 . 15003524 . 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 . Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease . Neuroscience . 121 . 2 . 307–14 . 2003 . 14521990 . 10.1016/S0306-4522(03)00438-X . 46593148 .
• Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y . 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 . 12721789 . 10.1007/s10038-003-0021-7 . free .
• Wu Z, Martin KO, Javitt NB, Chiang JY . Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1 . J. Lipid Res. . 40 . 12 . 2195–203 . 2000 . 10.1016/S0022-2275(20)32094-0 . 10588945 . free .

Notes and References

1. Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW . 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 . 9802883 . 509117 . 10.1172/JCI2962 .
2. 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 . Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration . Am J Hum Genet . 82 . 2 . 510–5 . Feb 2008 . 18252231 . 2426914 . 10.1016/j.ajhg.2007.10.001 .
3. Web site: Entrez Gene: CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1.
4. Stapleton G, Steel M, Richardson M, Mason JO, Rose KA, Morris RG, Lathe R . A novel cytochrome P450 expressed primarily in brain . J. Biol. Chem. . 270 . 50 . 29739–45 . December 1995 . 8530364 . 10.1074/jbc.270.50.29739 . free .
5. Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Björkhem I, Seckl J, Lathe R . 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 . 9144166 . 24607 . 10.1073/pnas.94.10.4925 . 1997PNAS...94.4925R . free .
6. Schwarz M, Lund EG, Lathe R, Björkhem I, Russell DW . Identification and characterization of a mouse oxysterol 7alpha-hydroxylase cDNA . J. Biol. Chem. . 272 . 38 . 23995–4001 . September 1997 . 9295351 . 10.1074/jbc.272.38.23995 . free .
7. Martin KO, Reiss AB, Lathe R, Javitt NB . 7 alpha-hydroxylation of 27-hydroxycholesterol: biologic role in the regulation of cholesterol synthesis . J. Lipid Res. . 38 . 5 . 1053–8 . May 1997 . 10.1016/S0022-2275(20)37229-1 . 9186922 . free .
8. Li-Hawkins J, Lund EG, Turley SD, Russell DW . Disruption of the oxysterol 7alpha-hydroxylase gene in mice . J. Biol. Chem. . 275 . 22 . 16536–42 . June 2000 . 10748048 . 10.1074/jbc.M001811200 . free .
9. Rose K, Allan A, Gauldie S, Stapleton G, Dobbie L, Dott K, Martin C, Wang L, Hedlund E, Seckl JR, Gustafsson JA, Lathe R . 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 . 11290741 . 10.1074/jbc.M011564200 . free.