“CYP27A1”的意思、由来-开放百科全书

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.^[1] 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.^[2]

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).^[3] Some marketed drugs that have been identified as CYP27A1 inhibitors include anastrozole, fadrozole, bicalutamide, dexmedetomidine, ravuconazole, and posaconazole.^[3]

Interactive pathway map

Further reading

{{cite journal | vauthors = Cali JJ, Russell DW | title = Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis | journal = The Journal of Biological Chemistry | volume = 266 | issue = 12 | pages = 7774–8 | date = April 1991 | pmid = 1708392 | doi = }}

{{cite journal | vauthors = Cali JJ, Hsieh CL, Francke U, Russell DW | title = Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis | journal = The Journal of Biological Chemistry | volume = 266 | issue = 12 | pages = 7779–83 | date = April 1991 | pmid = 2019602 | doi = }}

{{cite journal | vauthors = Guo YD, Strugnell S, Back DW, Jones G | title = Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 18 | pages = 8668–72 | date = September 1993 | pmid = 7690968 | pmc = 47419 | doi = 10.1073/pnas.90.18.8668 }}

{{cite journal | vauthors = Kim KS, Kubota S, Kuriyama M, Fujiyama J, Björkhem I, Eggertsen G, Seyama Y | title = Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX) | journal = Journal of Lipid Research | volume = 35 | issue = 6 | pages = 1031–9 | date = June 1994 | pmid = 7915755 | doi = }}

{{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}

{{cite journal | vauthors = Leitersdorf E, Reshef A, Meiner V, Levitzki R, Schwartz SP, Dann EJ, Berkman N, Cali JJ, Klapholz L, Berginer VM | title = Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin | journal = The Journal of Clinical Investigation | volume = 91 | issue = 6 | pages = 2488–96 | date = June 1993 | pmid = 8514861 | pmc = 443309 | doi = 10.1172/JCI116484 }}

{{cite journal | vauthors = Chen W, Kubota S, Kim KS, Cheng J, Kuriyama M, Eggertsen G, Björkhem I, Seyama Y | title = Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families | journal = Journal of Lipid Research | volume = 38 | issue = 5 | pages = 870–9 | date = May 1997 | pmid = 9186905 | doi = }}

{{cite journal | vauthors = Reiss AB, Martin KO, Rojer DE, Iyer S, Grossi EA, Galloway AC, Javitt NB | title = Sterol 27-hydroxylase: expression in human arterial endothelium | journal = Journal of Lipid Research | volume = 38 | issue = 6 | pages = 1254–60 | date = June 1997 | pmid = 9215552 | doi = }}

{{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}

{{cite journal | vauthors = Chen W, Kubota S, Ujike H, Ishihara T, Seyama Y | title = A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity | journal = Biochemistry | volume = 37 | issue = 43 | pages = 15050–6 | date = October 1998 | pmid = 9790667 | doi = 10.1021/bi9807660 }}

{{cite journal | vauthors = Shiga K, Fukuyama R, Kimura S, Nakajima K, Fushiki S | title = Mutation of the sterol 27-hydroxylase gene (CYP27) results in truncation of mRNA expressed in leucocytes in a Japanese family with cerebrotendinous xanthomatosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 67 | issue = 5 | pages = 675–7 | date = November 1999 | pmid = 10519880 | pmc = 1736608 | doi = 10.1136/jnnp.67.5.675 }}

{{cite journal | vauthors = Gascon-Barré M, Demers C, Ghrab O, Theodoropoulos C, Lapointe R, Jones G, Valiquette L, Ménard D | title = Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney | journal = Clinical Endocrinology | volume = 54 | issue = 1 | pages = 107–15 | date = Jan 2001 | pmid = 11167933 | doi = 10.1046/j.1365-2265.2001.01160.x }}

{{cite journal | vauthors = Johnston TP, Nguyen LB, Chu WA, Shefer S | title = Potency of select statin drugs in a new mouse model of hyperlipidemia and atherosclerosis | journal = International Journal of Pharmaceutics | volume = 229 | issue = 1–2 | pages = 75–86 | date = October 2001 | pmid = 11604260 | doi = 10.1016/S0378-5173(01)00834-1 }}

{{cite journal | vauthors = Toba H, Fukuyama R, Sasaki M, Shiga K, Ishibashi S, Fushiki S | title = A Japanese patient with cerebrotendinous xanthomatosis has different mutations within two functional domains of CYP27 | journal = Clinical Genetics | volume = 61 | issue = 1 | pages = 77–8 | date = Jan 2002 | pmid = 11903362 | doi = 10.1034/j.1399-0004.2002.610116.x }}

{{cite journal | vauthors = Lamon-Fava S, Schaefer EJ, Garuti R, Salen G, Calandra S | title = Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis | journal = Clinical Genetics | volume = 61 | issue = 3 | pages = 185–91 | date = March 2002 | pmid = 12000359 | doi = 10.1034/j.1399-0004.2002.610303.x }}

{{cite journal | vauthors = Björkhem I, Araya Z, Rudling M, Angelin B, Einarsson C, Wikvall K | title = 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 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 26804–7 | date = July 2002 | pmid = 12011083 | doi = 10.1074/jbc.M202343200 }}

{{cite journal | vauthors = von Bahr S, Movin T, Papadogiannakis N, Pikuleva I, Rönnow P, Diczfalusy U, Björkhem I | title = Mechanism of accumulation of cholesterol and cholestanol in tendons and the role of sterol 27-hydroxylase (CYP27A1) | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 22 | issue = 7 | pages = 1129–35 | date = July 2002 | pmid = 12117727 | doi = 10.1161/01.ATV.0000022600.61391.A5 }}

{{cite journal | vauthors = Meir K, Kitsberg D, Alkalay I, Szafer F, Rosen H, Shpitzen S, Avi LB, Staels B, Fievet C, Meiner V, Björkhem I, Leitersdorf E | title = Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis | journal = The Journal of Biological Chemistry | volume = 277 | issue = 37 | pages = 34036–41 | date = September 2002 | pmid = 12119285 | doi = 10.1074/jbc.M201122200 }}

{{cite journal | vauthors = Lee MJ, Huang YC, Sweeney MG, Wood NW, Reilly MM, Yip PK | title = Mutation of the sterol 27-hydroxylase gene ( CYP27A1) in a Taiwanese family with cerebrotendinous xanthomatosis | journal = Journal of Neurology | volume = 249 | issue = 9 | pages = 1311–2 | date = September 2002 | pmid = 12242561 | doi = 10.1007/s00415-002-0762-9 }}

Function

Clinical significance

Interactive pathway map

See also

References

Further reading

External links