Cytochrome P450 2A6 (CYP2A6)

Cytochrome P450 2A6 (CYP2A6) is a liver-expressed monooxygenase of the cytochrome P450 superfamily, catalyzing the oxidation of a wide variety of xenobiotics including nicotine, coumarin, pharmaceutical drugs, environmental carcinogens, and endogenous compounds like steroids and retinoic acids. It is the primary human enzyme for nicotine metabolism and the only one responsible for coumarin 7-hydroxylation. The gene encoding CYP2A6 is highly polymorphic, resulting in significant interindividual and interethnic variations in enzyme activity, which impacts drug metabolism, risk for nicotine addiction, cancer susceptibility, and therapeutic response. Numerous drugs inhibit or are metabolized by CYP2A6, resulting in clinically important drug interactions. The enzyme’s compact, hydrophobic active site determines its substrate specificity, and it is regulated by nuclear receptors and environmental factors. CYP2A6 is considered a promising target for interventions such as smoking cessation therapies and cancer prevention.

Other names

Cytochrome P450 family 2 subfamily A member 6CYP2A6human P450 2A6coumarin 7-hydroxylase

Enzymatic oxidation (hydroxylation) of small molecules; Metabolic activation or inactivation of drugs/procarcinogens; Inhibition of CYP2A6 to alter nicotine metabolism (for smoking cessation); Competitive and mechanism-based enzyme inhibition