The CYP2A6 is the only member of this subfamily that is expressed primarily in the liver and also may be expressed in lung and nasal
epithelium. It has a low level of hepatic expression and represents approximately 4% of the total hepatic CYP450 isoforms. It
catalyzes the 7-hydroxylation of coumarin (coumarin 7-hydroxylase), hydroxylation of aflatoxin B1, nicotine (C-oxidation to cotinine), naproxen, tacrine, clozapine, mexiletine, and cyclobenzaprine as well as the bioactivation of nitrosamines and procarcinogens. The
CYP2A6 exhibits polymorphism with an incidence of 2% in the Caucasian population. This population is characterized as poor
metabolizers. Smokers with a defective CYP2A6 gene smoke fewer cigarettes, implicating a genetic factor in nicotine dependence.
