TY - JOUR T1 - METABOLISM OF NICOTINE AND COTININE BY HUMAN CYTOCHROME P450 2A13 JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 258 LP - 261 DO - 10.1124/dmd.104.002105 VL - 33 IS - 2 AU - Ziping Bao AU - Xiao-Yang He AU - Xinxin Ding AU - Saileta Prabhu AU - Jun-Yan Hong Y1 - 2005/02/01 UR - http://dmd.aspetjournals.org/content/33/2/258.abstract N2 - Nicotine, a major constituent of tobacco, plays a critical role in smoking addiction. In humans, nicotine is primarily metabolized to cotinine, which is further metabolized to trans-3′-hydroxycotinine. Recently, we have demonstrated that heterologously expressed human CYP2A13 is highly active in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a nicotine-derived carcinogen. In the present study, CYP2A13-catalyzed NNK metabolism was found to be inhibited competitively by nicotine and N′-nitrosonornicotine (NNN), suggesting that both nicotine and NNN are also substrates of CYP2A13. We have further demonstrated that human CYP2A13 is indeed an efficient enzyme in catalyzing C-oxidation of nicotine to form cotinine, with the apparent Km and Vmax values of 20.2 μM and 8.7 pmol/min/pmol, respectively. CYP2A13 also catalyzes the 3′-hydroxylation of cotinine to form trans-3′-hydroxycotinine, with the apparent Km and Vmax values of 45.2 μM and 0.7 pmol/min/pmol, respectively. The importance of CYP2A13-catalyzed nicotine and cotinine metabolism in vivo remains to be determined. The American Society for Pharmacology and Experimental Therapeutics ER -