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Molecular Genetics of Nicotine Metabolism

  • Chapter
Book cover Nicotine Psychopharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 192))

Abstract

The molecular genetics of nicotine metabolism involves multiple polymorphic catalytic enzymes. Variation in metabolic pathways results in nicotine disposition kinetics that differ between individuals and ethnic groups. Twin studies indicate that a large part of this variance is genetic in origin, although environmental influences also contribute. The primary aim of this chapter is to review the current knowledge regarding the genetic variability in the enzymes that metabolize nicotine in humans. The focus is on describing the genetic polymorphisms that exist in cytochromes P450 (CYPs), aldehyde oxidase 1 (AOX1), UDP-glucuronosyltransferases (UGTs), and flavin-containing monooxygenase 3 (FMO3). Genetic studies have demonstrated that polymorphisms in CYP2A6, the primary enzyme responsible for nicotine breakdown, make a sizable contribution to the wide range of nicotine metabolic capacity observed in humans. Thus, special attention will be given to CYP2A6, because slower nicotine metabolism requires less frequent self-administration, and accordingly influences smoking behaviors. In addition, the molecular genetics of nicotine metabolism in nonhuman primates, mice, and rats will be reviewed briefly.

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Authors and Affiliations

  1. Centre for Addiction & Mental Health and Department of Pharmacology, University of Toronto, Toronto, ON, Canada

    Jill C. Mwenifumbo

  2. Center for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Rm 4326 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada

    Rachel F. Tyndale

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  1. Jill C. Mwenifumbo
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  1. Pinney Associates, 3 Bethesda Metro Center, Bethesda, MD, 20814-3472, USA

    Jack E. Henningfield

  2. UCLA Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA, 90024-1759, USA

    Edythe D. London

  3. Center for Brain Research, Bornova, Ege University, Izmir, 35100, Turkey

    Sakire Pogun

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Mwenifumbo, J.C., Tyndale, R.F. (2009). Molecular Genetics of Nicotine Metabolism. In: Henningfield, J.E., London, E.D., Pogun, S. (eds) Nicotine Psychopharmacology. Handbook of Experimental Pharmacology, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69248-5_9

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