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  • Title: Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.
    Author: Zhang X, Ameno K, Ameno S, Kinoshita H, Kubota T, Kumihashi M, Mostofa J, Iwahashi K, Ijiri I.
    Journal: Drug Chem Toxicol; 2002 May; 25(2):203-13. PubMed ID: 12024803.
    Abstract:
    We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3'-hydroxylating resulted in trans-3'-hydroxycotinine formation. In the subjects genotyped by PCR-RFLP method, one cigarette smoking experiment was performed and urine samples were collected for 24 h. In all subjects who smoked, we detected nicotine, cotinine and trans-3'-hydroxycotinine in urine by GC-MS analysis. In whole deletion of CYP2A6, urinary excretion amounts of cotinine and trans-3'-hydroxycotinine were significantly smaller than those in the wild-type of CYP2A6*1. A lack of CYP2A6 reduces the formation of cotinine and trans-3'-hydroxycotinine, but not entirely reduces the trans-3'-hydroxycotinine formation. Unknown cotinine 3'-hydroxylating activity except CYP2A6 are suspected in humans.
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