Biology:CYP27A1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the mitochondria. It is most prominently involved in the biosynthesis of bile acids.

Function

CYP27A1 participates in the degradation of cholesterol to bile acids in both the classic and acidic pathways. It is the initiating enzyme in the acidic pathway to bile acids, yielding oxysterols by introducing a hydroxyl group to the carbon at the 27 position in cholesterol. In the acidic pathway, it produces 27-hydroxycholesterol from cholesterol whereas in the classic or neutral pathway, it produces 3β-hydroxy-5-cholestenoic acid.

While CYP27A1 is present in many different tissues, its function in these tissues is largely uncharacterized. In macrophages, 27-hydroxycholesterol generated by this enzyme may be helpful against the production of inflammatory factors associated with cardiovascular disease.

Clinical significance

Mutations in CYP27A1 are associated with cerebrotendineous xanthomatosis, a rare lipid storage disease.

Inhibitors of CYP27A1 may be effective as adjuvants in the treatment of ER-positive breast cancer due to inhibition of the production of 27-hydroxycholesterol (which has estrogenic actions and stimulates the growth of ER-positive breast cancer cells). Some marketed drugs that have been identified as CYP27A1 inhibitors include anastrozole, fadrozole, bicalutamide, dexmedetomidine, ravuconazole, and posaconazole.

See also

• Steroidogenic enzyme
• CYP27 family

Further reading

• "Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis". The Journal of Biological Chemistry 266 (12): 7774–8. April 1991. doi:10.1016/S0021-9258(20)89517-9. PMID 1708392. 
• "Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis". The Journal of Biological Chemistry 266 (12): 7779–83. April 1991. doi:10.1016/S0021-9258(20)89518-0. PMID 2019602. 
• "Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions". Proceedings of the National Academy of Sciences of the United States of America 90 (18): 8668–72. September 1993. doi:10.1073/pnas.90.18.8668. PMID 7690968. Bibcode: 1993PNAS...90.8668G. 
• "Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)". Journal of Lipid Research 35 (6): 1031–9. June 1994. doi:10.1016/S0022-2275(20)40096-3. PMID 7915755. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. Jan 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin". The Journal of Clinical Investigation 91 (6): 2488–96. June 1993. doi:10.1172/JCI116484. PMID 8514861. 
• "Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families". Journal of Lipid Research 38 (5): 870–9. May 1997. doi:10.1016/S0022-2275(20)37212-6. PMID 9186905. 
• "Sterol 27-hydroxylase: expression in human arterial endothelium". Journal of Lipid Research 38 (6): 1254–60. June 1997. doi:10.1016/S0022-2275(20)37206-0. PMID 9215552. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity". Biochemistry 37 (43): 15050–6. October 1998. doi:10.1021/bi9807660. PMID 9790667. 
• "Mutation of the sterol 27-hydroxylase gene (CYP27) results in truncation of mRNA expressed in leucocytes in a Japanese family with cerebrotendinous xanthomatosis". Journal of Neurology, Neurosurgery, and Psychiatry 67 (5): 675–7. November 1999. doi:10.1136/jnnp.67.5.675. PMID 10519880. 
• "Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney". Clinical Endocrinology 54 (1): 107–15. Jan 2001. doi:10.1046/j.1365-2265.2001.01160.x. PMID 11167933. 
• "Potency of select statin drugs in a new mouse model of hyperlipidemia and atherosclerosis". International Journal of Pharmaceutics 229 (1–2): 75–86. October 2001. doi:10.1016/S0378-5173(01)00834-1. PMID 11604260. 
• "A Japanese patient with cerebrotendinous xanthomatosis has different mutations within two functional domains of CYP27". Clinical Genetics 61 (1): 77–8. Jan 2002. doi:10.1034/j.1399-0004.2002.610116.x. PMID 11903362. 
• "Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis". Clinical Genetics 61 (3): 185–91. March 2002. doi:10.1034/j.1399-0004.2002.610303.x. PMID 12000359. 
• "Differences in the regulation of the classical and the alternative pathway for bile acid synthesis in human liver. No coordinate regulation of CYP7A1 and CYP27A1". The Journal of Biological Chemistry 277 (30): 26804–7. July 2002. doi:10.1074/jbc.M202343200. PMID 12011083. 
• "Mechanism of accumulation of cholesterol and cholestanol in tendons and the role of sterol 27-hydroxylase (CYP27A1)". Arteriosclerosis, Thrombosis, and Vascular Biology 22 (7): 1129–35. July 2002. doi:10.1161/01.ATV.0000022600.61391.A5. PMID 12117727. 
• "Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis". The Journal of Biological Chemistry 277 (37): 34036–41. September 2002. doi:10.1074/jbc.M201122200. PMID 12119285. 
• "Mutation of the sterol 27-hydroxylase gene ( CYP27A1) in a Taiwanese family with cerebrotendinous xanthomatosis". Journal of Neurology 249 (9): 1311–2. September 2002. doi:10.1007/s00415-002-0762-9. PMID 12242561. 

External links

• GeneReviews/NCBI/NIH/UW entry on Cerebrotendinous Xanthomatosis
• Cytochrome+P-450+CYP27A1 at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human CYP27A1 genome location and CYP27A1 gene details page in the UCSC Genome Browser.