The CYP2A6 enzyme accounts for the vast majority of the metabolism of nicotine to cotinine, with minor contributions from CYP2B6, CYP2D6, and CYP2E1 enzymes (Messina et al., 1997; Nakajima et al., 1996; Yamanaka et al., 2005; Yamazaki et al., 1999). CYP2B6 has an approximately 10% catalytic efficiency of the CYP2A6 enzyme in vitro in nicotine c-oxidation, and it might play a minor role in nicotine clearance at higher nicotine levels or in CYP2A6 genetically impaired individuals (Benowitz et al., 2006b; Yamazaki et al., 1999). While CYP2A6 is expressed primarily in the liver, CYP2B6 is expressed at higher levels in the brain, where it may influence highly localized metabolism of nicotine in the brains of human smokers (Miksys et al., 2003).
