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Cytochrome P450, family 2, subfamily A, polypeptide 6

PDB rendering based on 1z10.
Available structures
1z10, 1z11, 2fdu, 2fdv, 2fdw, 2fdy, 2p85
Identifiers
Symbols CYP2A6; CYP2A; P450C2A; P450PB; CPA6; CYP2A3; CPA7; CPAD; CYPIIA7; P450-IIA4
External IDs OMIM122720 HomoloGene86656 GeneCards: CYP2A6 Gene
Orthologs
Species Human Mouse
Entrez 1548 n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) NM_000762 n/a
RefSeq (protein) NP_000753 n/a
Location (UCSC) n/a n/a
PubMed search [1] n/a

Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and cotinine. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of coumarin, such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.

The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.[1]

Contents

Distribution

CYP2A6 localizes to the endoplasmic reticulum and is found predominantly in the liver.

Variability

Significant interindividual variability in CYP2A6 apoprotein and mRNA levels has been observed.

Induction

CYP2A6 is known to be inducible by phenobarbital and rifampicin, and it is suspected that other antiepileptic drugs may also have this effect.

CYP2A6 Ligands

Selected inducers, inhibitors and substrates of CYP2A6
Substrates Inhibitors Inducers

References

Further reading

  • Pelkonen O, Rautio A, Raunio H, Pasanen M (2000). "CYP2A6: a human coumarin 7-hydroxylase". Toxicology 144 (1-3): 139–47. doi:10.1016/S0300-483X(99)00200-0. PMID 10781881.  
  • Fernandez-Salguero P, Gonzalez FJ (1995). "The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis.". Pharmacogenetics 5 Spec No: S123–8. doi:10.1097/00008571-199512001-00013. PMID 7581481.  
  • Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily.". Xenobiotica 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.  
  • Pelkonen O, Rautio A, Raunio H, Pasanen M (2000). "CYP2A6: a human coumarin 7-hydroxylase.". Toxicology 144 (1-3): 139–47. doi:10.1016/S0300-483X(99)00200-0. PMID 10781881.  
  • Tyndale RF, Sellers EM (2002). "Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior.". Therapeutic drug monitoring 24 (1): 163–71. doi:10.1097/00007691-200202000-00026. PMID 11805739.  
  • Xu C, Goodz S, Sellers EM, Tyndale RF (2003). "CYP2A6 genetic variation and potential consequences.". Adv. Drug Deliv. Rev. 54 (10): 1245–56. doi:10.1016/S0169-409X(02)00065-0. PMID 12406643.  
  • Kamataki T, Fujieda M, Kiyotani K, et al. (2005). "Genetic polymorphism of CYP2A6 as one of the potential determinants of tobacco-related cancer risk.". Biochem. Biophys. Res. Commun. 338 (1): 306–10. doi:10.1016/j.bbrc.2005.08.268. PMID 16176798.  
  • Maurice M, Emiliani S, Dalet-Beluche I, et al. (1991). "Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes.". Eur. J. Biochem. 200 (2): 511–7. doi:10.1111/j.1432-1033.1991.tb16212.x. PMID 1889415.  
  • Yun CH, Shimada T, Guengerich FP (1991). "Purification and characterization of human liver microsomal cytochrome P-450 2A6.". Mol. Pharmacol. 40 (5): 679–85. PMID 1944238.  
  • Yamano S, Tatsuno J, Gonzalez FJ (1990). "The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes.". Biochemistry 29 (5): 1322–9. doi:10.1021/bi00457a031. PMID 2322567.  
  • Miles JS, Bickmore W, Brook JD, et al. (1989). "Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity.". Nucleic Acids Res. 17 (8): 2907–17. doi:10.1093/nar/17.8.2907. PMID 2726448.  
  • Yamano S, Nagata K, Yamazoe Y, et al. (1989). "cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3).". Nucleic Acids Res. 17 (12): 4888. doi:10.1093/nar/17.12.4888. PMID 2748347.  
  • Phillips IR, Shephard EA, Ashworth A, Rabin BR (1985). "Isolation and sequence of a human cytochrome P-450 cDNA clone.". Proc. Natl. Acad. Sci. U.S.A. 82 (4): 983–7. doi:10.1073/pnas.82.4.983. PMID 3856261.  
  • Wainwright BJ, Watson EK, Shephard EA, Phillips IR (1985). "RFLP for a human cytochrome P-450 gene at 19q13.1-qter (HGM8 provisional designation CYPI).". Nucleic Acids Res. 13 (12): 4610. doi:10.1093/nar/13.12.4610. PMID 4011450.  
  • Fernandez-Salguero P, Hoffman SM, Cholerton S, et al. (1995). "A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles.". Am. J. Hum. Genet. 57 (3): 651–60. PMID 7668294.  
  • Ding S, Lake BG, Friedberg T, Wolf CR (1995). "Expression and alternative splicing of the cytochrome P-450 CYP2A7.". Biochem. J. 306 ( Pt 1): 161–6. PMID 7864805.  
  • Hoffman SM, Fernandez-Salguero P, Gonzalez FJ, Mohrenweiser HW (1996). "Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19.". J. Mol. Evol. 41 (6): 894–900. PMID 8587134.  
  • Hadidi H, Zahlsen K, Idle JR, Cholerton S (1998). "A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin.". Food Chem. Toxicol. 35 (9): 903–7. PMID 9409631.  
  • Oscarson M, Gullstén H, Rautio A, et al. (1998). "Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase.". FEBS Lett. 438 (3): 201–5. doi:10.1016/S0014-5793(98)01297-6. PMID 9827545.  
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