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Cyp27a1

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Cyp27a1

Cytochrome P450, family 27, subfamily A, polypeptide 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; CP27; CTX; CYP27
External IDs ChEMBL: GeneCards:
EC number
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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.

Contents

  • Function 1
  • Clinical significance 2
  • Interactive pathway map 3
  • References 4
  • Further reading 5
  • External links 6

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.

It is also involved in the metabolism of vitamin D3.[2]

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.[3]

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).[4] Some marketed drugs that have been identified as CYP27A1 inhibitors include anastrozole, fadrozole, bicalutamide, dexmedetomidine, ravuconazole, and posaconazole.[4]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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Vitamin D Synthesis Pathway edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531". 

References

  1. ^ Chiang JY (February 1998). "Regulation of bile acid synthesis". Front Biosci 3: d176–193.  
  2. ^ Sakaki T, Kagawa N, Yamamoto K, Inouye K (January 2005). by cytochromes P450"3"Metabolism of vitamin D. Front. Biosci. 10: 119–34.  
  3. ^ Taylor JM, Borthwick F, Bartholomew C, Graham A (June 2010). "Overexpression of steroidogenic acute regulatory protein increases macrophage cholesterol efflux to apolipoprotein AI". Cardiovasc Res 86 (3): 526–534.  
  4. ^ a b Mast N, Lin JB, Pikuleva IA (2015). "Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy". Mol. Pharmacol. 88 (3): 428–36.  

Further reading

  • Cali JJ, Russell DW (1991). "Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis.". J. Biol. Chem. 266 (12): 7774–8.  
  • Cali JJ, Hsieh CL, Francke U, Russell DW (1991). "Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis.". J. Biol. Chem. 266 (12): 7779–83.  
  • Guo YD, Strugnell S, Back DW, Jones G (1993). "Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions.". Proc. Natl. Acad. Sci. U.S.A. 90 (18): 8668–72.  
  • Kim KS, Kubota S, Kuriyama M, et al. (1994). "Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)". J. Lipid Res. 35 (6): 1031–9.  
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4.  
  • Leitersdorf E, Reshef A, Meiner V, et al. (1993). "Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin". J. Clin. Invest. 91 (6): 2488–96.  
  • Chen W, Kubota S, Kim KS, et al. (1997). "Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families". J. Lipid Res. 38 (5): 870–9.  
  • Reiss AB, Martin KO, Rojer DE, et al. (1997). "Sterol 27-hydroxylase: expression in human arterial endothelium". J. Lipid Res. 38 (6): 1254–60.  
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56.  
  • Chen W, Kubota S, Ujike H, et al. (1998). "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.  
  • Shiga K, Fukuyama R, Kimura S, et al. (1999). "Mutation of the sterol 27-hydroxylase gene (CYP27) results in truncation of mRNA expressed in leucocytes in a Japanese family with cerebrotendinous xanthomatosis". J. Neurol. Neurosurg. Psychiatr. 67 (5): 675–7.  
  • Gascon-Barré M, Demers C, Ghrab O, et al. (2001). "Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney". Clin. Endocrinol. (Oxf) 54 (1): 107–15.  
  • Johnston TP, Nguyen LB, Chu WA, Shefer S (2001). "Potency of select statin drugs in a new mouse model of hyperlipidemia and atherosclerosis". International journal of pharmaceutics 229 (1–2): 75–86.  
  • Toba H, Fukuyama R, Sasaki M, et al. (2002). "A Japanese patient with cerebrotendinous xanthomatosis has different mutations within two functional domains of CYP27". Clin. Genet. 61 (1): 77–8.  
  • Lamon-Fava S, Schaefer EJ, Garuti R, et al. (2002). "Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis". Clin. Genet. 61 (3): 185–91.  
  • Björkhem I, Araya Z, Rudling M, et al. (2002). "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". J. Biol. Chem. 277 (30): 26804–7.  
  • von Bahr S, Movin T, Papadogiannakis N, et al. (2002). "Mechanism of accumulation of cholesterol and cholestanol in tendons and the role of sterol 27-hydroxylase (CYP27A1)". Arterioscler. Thromb. Vasc. Biol. 22 (7): 1129–35.  
  • Meir K, Kitsberg D, Alkalay I, et al. (2002). "Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis". J. Biol. Chem. 277 (37): 34036–41.  
  • Lee MJ, Huang YC, Sweeney MG, et al. (2002). "Mutation of the sterol 27-hydroxylase gene ( CYP27A1) in a Taiwanese family with cerebrotendinous xanthomatosis". J. Neurol. 249 (9): 1311–2.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903.  

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)
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