The CYP2A6 gene, which codes the enzyme, has known to have ahigh polymorphism. This polymorphism could decrease, increase, or eliminate enzyme activity. CYP2A6*4 , an inactive allele, decreased One of enzyme-specific substrates is nicotine. allele decrease nicotine metabolism that causes high levels in blood. In addition, it caused increasing Low-Density Lipoprotein Cholesterol (LDL-C) by expan...

Cytochrome P450 (CYP) is a superfamily of enzymes involved in the metabolism of endogenous compounds and xenobiotics. CYP2A6 catalyzes the oxidation of nicotine and the activation of carcinogens such as aflatoxin B1 and nitrosamines. CYP2E1 metabolizes ethanol and other low-molecular weight compounds and can also activate nitrosamines. The CYP2A6 and CYP2E1 genes are polymorphic, altering their...

Over the past decade interest in the biochemical and biological properties of polyphenols has grown considerably, as epidemiological evidence for their beneficial effects on health continues to increase. Dietary polyphenol antioxidants are reported to have many ‘health promoting’ properties, including anti-inflammatory, vasoprotection, anti-cancer and anti-obesity effects. However, their absorp...

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...

Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens. CYP2A6 genetic variants have been associated with smoking status, cigarette consumption, and tobacco-related cancers. Our objective was to functionally characterize four nonsynonymous CYP2A6 sequence variants with respect to thei...

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 microg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 microg/g creatinine. Average age and Cd burden of women and ...

Human CYP2A6 is responsible for the metabolism of nicotine and its genetic polymorphisms affect smoking behavior and risk of lung cancer. In the present study, we identified a novel type of CYP2A6 gene duplication that is created through an unequal crossover event with the CYP2A7 gene at 5.2 to 5.6 kilobases downstream from the stop codon. The novel duplication type of CYP2A6 was found in Afric...

Background: Cytochrome P450 2A13 (CYP2A13) and 2A6 (CYP2A6) are enzymes expressed in the human respiratory tract, exhibit high efficiency in the metabolic activation of tobacco carcinogen 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A C→T transition in the CYP2A13 gene causes Arg257Cys amino acid substitution and a deletion of the CYP2A6 gene named as CYP2A6 *4, both of them result in a...

PHARMACOKINETIC POPULATION MODELING OF NICOTINE INCORPORATING CYP2A6 GENOTYPES FOLLOWING DIFFERENT ROUTES OF ADMINISTRATION. Y. Yoon, MD, PhD, D. Verotta, PhD, N. Benowitz, MD, University of California San Francisco, Inje University (Korea), San Francisco, CA. PURPOSE: We developed a comprehensive population pharmacokinetic (PK) model to quantify the influence of CYP2A6 genetic polymorphisms (G...

While smoking is the primary cause of lung cancer, only 11-24% of smokers develop the malignancy over their lifetime. The primary addictive agent in tobacco smoke is nicotine and variation in nicotine metabolism may influence the smoking levels of an individual. Therefore, inter-individual variation in lung cancer risk among smokers may be due in part to differences in the activity of enzymes i...