Metabolism of nicotine and cotinine by human cytochrome P450 2A13

Ziping Bao, Xiao Yang He, Xinxin Ding, Saileta Prabhu, Jun Yan Hong

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)258-261
Number of pages4
JournalDrug Metabolism and Disposition
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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