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.
^ abcdefghijklmnopqrstuvwxyzaaabacadLacy CF, Armstrong LL, Goldman MP, Lance LL (2007). Cytochrome P450 Enzymes: Substrates, Inhibitors, and Inducers. Hudson, OH: LexiComp Inc. pp. 1899–1912.
^Wen X, Wang JS, Neuvonen PJ, Backman JT (2002). "Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes". Eur. J. Clin. Pharmacol.57 (11): 799–804. doi:10.1007/s00228-001-0396-3. PMID11868802.
^Siu EC, Tyndale RF (2008). "Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice". J. Pharmacol. Exp. Ther.324 (3): 992–9. doi:10.1124/jpet.107.133900. PMID18065502.
Fernandez-Salguero P, Gonzalez FJ (1995). "The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis". Pharmacogenetics5 (Special Issue): S123–8. doi:10.1097/00008571-199512001-00013. PMID7581481.
Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica28 (12): 1129–65. doi:10.1080/004982598238868. PMID9890157.
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. PMID16176798.
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. PMID1889415.
Yun CH, Shimada T, Guengerich FP (1991). "Purification and characterization of human liver microsomal cytochrome P-450 2A6". Mol. Pharmacol.40 (5): 679–85. PMID1944238.
Yamano S, Tatsuno J, Gonzalez FJ (1990). "The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes". Biochemistry29 (5): 1322–9. doi:10.1021/bi00457a031. PMID2322567.
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. doi:10.1007/bf00173169. PMID8587134.
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. doi:10.1016/S0278-6915(97)00066-5. PMID9409631.