Genetically determined metabolism of nicotine and its clinical significance

Marcin Delijewski; Aleksandra Bartoń; Paulina Delijewska; Radosław Balwierz; Grzegorz Jakubiak; Leon Kośmider; Natalia Pawlas

doi:10.18388/abp.2019_2645

Marcin Delijewski Department of Pharmacology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland https://orcid.org/0000-0001-7425-9865
Aleksandra Bartoń Department of Pharmacology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland https://orcid.org/0000-0001-7339-0642
Paulina Delijewska Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland https://orcid.org/0000-0002-3184-1481
Radosław Balwierz Silesian Medical College in Katowice, Mickiewicza 29, Katowice 40-085, Poland https://orcid.org/0000-0002-6173-2702
Grzegorz Jakubiak Department of Pharmacology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland https://orcid.org/0000-0003-0039-8306
Leon Kośmider Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University and Affiliated with Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, VA, USA https://orcid.org/0000-0001-7837-9813
Natalia Pawlas Department of Pharmacology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland https://orcid.org/0000-0002-7551-9371

DOI: https://doi.org/10.18388/abp.2019_2645

Abstract

Enzymes of the cytochrome P-450 (CYP 450) which belong to the family of oxidase enzymes, are present in cells of all organisms and play a major role in the first phase of xenobiotic metabolism. There are several isoenzymes of CYP 450 that show differences in the speed of metabolism: poor-, extensive- and ultra-rapid. Nicotine undergoes biotransformation in the liver mainly by the CYP2A6 isoform of CYP 450. There are many polymorphic isoforms of CYP2A6 affecting the metabolism of nicotine. There are also several CYP2A6 activity inhibitors and inducers among commonly used drugs. The ability of CYP2A6 isozymes to activate certain procancerogenic substances present in cigarette smoke makes their polymorphism more significant. Moreover, some isoforms may have also influence on the risk of lung cancer development by affecting the enzymatic activation of tobacco-specific nitrosamines. Metabolism of nicotine, mainly through CYP2A6, has also many clinical implications, such as efficacy and safety of the nicotine replacement therapy (NRT) or occurrence of several diseases. In summary, type of the nicotine metabolism may be a potential predictor of the clinical outcomes in patients with cardiovascular disease, addicted to nicotine and in those using NRT. The purpose of this work is to summarize current knowledge on variation in genetically determined metabolism of nicotine and its clinical significance.

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