Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism

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CYP2A6 gene polymorphisms impact to nicotine metabolism

Nicotine is a major addictive compound in tobacco cigarette smoke. After being absorbed by the lung nicotine is rapidly metabolized and mainly inactivated to cotinine by hepatic cytochrome P450 2A6 (CYP2A6) enzyme. Genetic polymorphisms in CYP2A6 may play a role in smoking behavior and nicotine dependence. CYP2A6*1A is the wild type of the CYP2A6 gene which is associated with normal or extensiv...

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Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism.

During the last couple of years, cytochrome P450 2A6 (CYP2A6; coumarin 7-hydroxylase) has received a lot of attention because it has been shown that it is the principle human nicotine C-oxidase. This enzyme also activates a number of structurally unrelated precarcinogens including many nitrosamines and aflatoxin B1, and metabolizes certain clinically used drugs. There is a pronounced interindiv...

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CYP2A6 Polymorphisms May Strengthen Individualized Treatment for Nicotine Dependence

Each CYP2A6 gene variant metabolizes nicotine differently depending on its enzymatic activities. The normal nicotine metabolizer CYP2A6(*)1A is associated with high scores of nicotine dependence (5-10) on the Fagerström Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and...

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Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk.

Nicotine is the psychoactive substance responsible for tobacco dependence; smokers adjust their cigarette consumption to maintain brain nicotine levels. In humans, 70 to 80% of nicotine is metabolized to the inactive metabolite cotinine by the enzyme CYP2A6. CYP2A6 can also activate tobacco smoke procarcinogens [e.g., NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. In initial studies we f...

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Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism.

Nicotine is the major addictive agent in tobacco. The primary catalyst of nicotine metabolism in humans is CYP2A6. However, the closely related enzyme CYP2A13 is a somewhat better catalyst. CYP2A13 is an extrahepatic enzyme that is an excellent catalyst of the metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK). Here we report that both C...

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ژورنال

عنوان ژورنال: British Journal of Clinical Pharmacology

سال: 2002

ISSN: 0306-5251

DOI: 10.1046/j.1365-2125.2002.01667.x