PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34520119-0 2021 Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 45-51 34476898-1 2022 CYP2A6 activity, phenotyped by the nicotine metabolite ratio (NMR), is a predictor of several smoking behaviours, including cessation and smoking-related disease risk. Nicotine 35-43 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 34520119-3 2021 The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. Nicotine 102-110 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 43-49 34520119-3 2021 The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. Nicotine 102-110 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 72-78 34576282-1 2021 Cytochrome P450 (CYP) 2A6 is a monooxygenase involved in the metabolism of various endogenous and exogenous chemicals, such as nicotine and therapeutic drugs. Nicotine 127-135 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-25 34165800-3 2021 Candidate gene studies of smoking phenotypes have identified several pharmacogenes implicated in nicotine"s pharmacokinetics (CYP2A6, CYP2B6, CYP2A13, FMOs, UGTs, and OCT2), and nicotine"s pharmacodynamic response in the central nervous system (nicotinic acetylcholine receptors, as well as through the dopaminergic and serotonergic systems). Nicotine 97-105 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 126-132 34478556-0 2022 Nicotine metabolism predicted by CYP2A6 genotypes in relation to smoking cessation: A systematic review. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-39 34478556-2 2022 Of major interest is genetic variation in nicotine metabolism, largely predicted by CYP2A6 variations. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 34478556-3 2022 METHODS: We conducted a systematic literature review to summarize the population-based evidence of the association between CYP2A6 and smoking cessation.In the 12 studies meeting the inclusion criteria, the known functional metabolic effect of CYP2A6 variants was used to classify nicotine metabolism as normal (>75% metabolic activity), intermediate (50.1 - 75% activity), slow (25 - 50% activity), and poor (<25% activity). Nicotine 280-288 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 243-249 34478556-5 2022 RESULTS: Among untreated people of European ancestry (n = 4 studies), those with CYP2A6 reduced metabolism were more likely to quit smoking than those with normal metabolism (Summary OR = 2.05, 95% CI 1.23 - 3.42) and the likelihood of cessation increased as nicotine metabolism decreased. Nicotine 259-267 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 81-87 34165800-7 2021 The genes CYP2A6 and the CHRNA5-A3-B4 confer the most replicated sources of genetic variation in smoking behaviours, likely due to their importance in nicotine"s pharmacology. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 33329709-0 2020 Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation. Nicotine 112-120 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 94-100 35427216-1 2022 CYP2A6 is a very important enzyme that plays a crucial role in nicotine compounds and is responsible for the metabolism of more than 3% drugs of total metabolized drugs by the CYP family and reported as one of very important pharmacogenes. Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 35197312-1 2022 The major mode of metabolism of nicotine is via the formation of cotinine by the enzyme cytochrome P450 (CYP) 2A6. Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-113 33375250-2 2020 One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 50-75 33375250-2 2020 One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 50-75 33375250-3 2020 Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 7-13 32496054-5 2020 Additionally, there is significant genetic variability in rate of metabolism of nicotine due to polymorphisms of CYP2A6, the enzyme responsible for the metabolism of approximately 80% of nicotine. Nicotine 80-88 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 32496054-5 2020 Additionally, there is significant genetic variability in rate of metabolism of nicotine due to polymorphisms of CYP2A6, the enzyme responsible for the metabolism of approximately 80% of nicotine. Nicotine 187-195 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 32496054-6 2020 Recent studies have shown CYP2A6 is also readily inhibited by aromatic aldehydes such as those added to e-cigarette liquids as flavoring agents, which may increase nicotine serum concentrations. Nicotine 164-172 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 26-32 32496054-7 2020 However, the impacts of e-cigarette flavorings on metabolism of nicotine by CYP2A6 activity are unknown. Nicotine 64-72 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 76-82 32496054-13 2020 These data indicate certain aromatic aldehyde flavoring agents are potent inhibitors of CYP2A6, which may reduce nicotine metabolism in vivo. Nicotine 113-121 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-94 31578905-2 2020 While the liver-specific CYP2A6 is associated with the nicotine clearance and smoking addiction, the metabolic activation of the tobacco-specific nitrosamine by lung-specific CYP2A13 can lead to lung tumorigenesis. Nicotine 55-63 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 32350062-2 2020 CYP2A6 is responsible for the metabolism of nicotine and several other xenobiotics, but its susceptibility to down-regulation by NO has not been reported. Nicotine 44-52 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 32350062-12 2020 SIGNIFICANCE STATEMENT: This study demonstrates that the nicotine metabolizing enzyme CYP2A6 is down regulated by nitric oxide, a molecule produced in large amounts in the context of inflammation and that is also inhaled from cigarette smoke. Nicotine 57-65 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 86-92 32131765-1 2020 BACKGROUND: CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). Nicotine 104-112 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 29788791-1 2018 INTRODUCTION: It has been suggested that the effectiveness of nicotine replacement smoking cessation pharmacotherapy may be enhanced by assessing rates of nicotine metabolism using the nicotine metabolite ratio - which reflects differences in the activity of the CYP2A6 hepatic enzyme - and titrating doses appropriately. Nicotine 62-70 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 263-269 31628204-0 2020 The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice. Nicotine 46-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 31628204-1 2020 During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by CYP2A6. Nicotine 36-44 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 89-95 31628204-2 2020 Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Nicotine 93-101 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 20-26 31628204-2 2020 Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Nicotine 270-278 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 161-167 31584787-3 2019 Nicotine undergoes biotransformation in the liver mainly by the CYP2A6 isoform of CYP 450. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 31584787-4 2019 There are many polymorphic isoforms of CYP2A6 affecting the metabolism of nicotine. Nicotine 74-82 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 31584787-8 2019 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. Nicotine 14-22 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 31584787-8 2019 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. Nicotine 119-127 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 30381441-1 2019 BACKGROUND: The major mode of metabolism of nicotine is by hydroxylation via cytochrome P450 (CYP) 2A6, but it can also undergo glucuronidation by UDP-glucuronosyltransferases and oxidation by flavin monooxygenases (FMO). Nicotine 44-52 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 77-102 30381441-8 2019 CONCLUSIONS: These data indicate that increases in nicotine-N"-oxidation occur in subjects with deficient CYP2A6 activity, and that several FMO enzymes are active in nicotine-N"-oxidation. Nicotine 51-59 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 106-112 30381441-9 2019 IMPACT: Several common missense FMO variants are associated with altered enzyme activity against nicotine and may play an important role in nicotine metabolism in low-CYP2A6 activity subjects. Nicotine 97-105 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 167-173 30381441-9 2019 IMPACT: Several common missense FMO variants are associated with altered enzyme activity against nicotine and may play an important role in nicotine metabolism in low-CYP2A6 activity subjects. Nicotine 140-148 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 167-173 31453782-1 2019 BACKGROUND: Cytochrome P450 2A6 enzyme (CYP2A6), an essential hepatic enzyme involved in the metabolism of drugs, is responsible for a major metabolic pathway of nicotine. Nicotine 162-170 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-31 31453782-1 2019 BACKGROUND: Cytochrome P450 2A6 enzyme (CYP2A6), an essential hepatic enzyme involved in the metabolism of drugs, is responsible for a major metabolic pathway of nicotine. Nicotine 162-170 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 40-46 31453782-2 2019 Variation in the activity of polymorphic CYP2A6 alleles has been implicated in inter-individual differences in nicotine metabolism. Nicotine 111-119 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 41-47 30815984-1 2020 The nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is an index of CYP2A6 activity. Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 79-85 30815984-2 2020 CYP2A6 is responsible for nicotine"s metabolic inactivation and variation in the NMR/CYP2A6 is associated with several smoking behaviors. Nicotine 26-34 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 30611298-4 2019 As cotinine levels are influenced not only by nicotine intake but also by CYP2A6-mediated nicotine metabolism rate, we performed secondary analyses adjusting for genetic risk score of nicotine metabolism rate and identified five additional novel associations. Nicotine 90-98 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 74-80 30611298-4 2019 As cotinine levels are influenced not only by nicotine intake but also by CYP2A6-mediated nicotine metabolism rate, we performed secondary analyses adjusting for genetic risk score of nicotine metabolism rate and identified five additional novel associations. Nicotine 90-98 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 74-80 29995408-2 2018 The development of a specific inhibitor of cytochrome P450 2A6 (CYP2A6), the major nicotine-metabolizing enzyme in humans, which could be prescribed for the cessation of cigarette smoking, has been undertaken. Nicotine 83-91 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 43-62 29995408-2 2018 The development of a specific inhibitor of cytochrome P450 2A6 (CYP2A6), the major nicotine-metabolizing enzyme in humans, which could be prescribed for the cessation of cigarette smoking, has been undertaken. Nicotine 83-91 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 29158210-9 2018 In conclusion, pregnancy-induced increases in nicotine metabolism start by 12 weeks gestation and continue as pregnancy progresses most likely due to induction of CYP2A6 and UGT2B10, resulting in potential reductions in the effectiveness of nicotine replacement therapies and an increase in metabolism of other CYP2A6 and UGT2B10 substrates during pregnancy. Nicotine 46-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 163-169 29158210-7 2018 The CYP2A6 phenotype ratio (total 3"-hydroxycotinine/cotinine) was significantly higher at early and late pregnancy compared with postpartum (all P < 0.05) and correlated with nicotine C-oxidation (all P < 0.001), suggesting CYP2A6 activity is induced during pregnancy. Nicotine 179-187 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 4-10 29158210-7 2018 The CYP2A6 phenotype ratio (total 3"-hydroxycotinine/cotinine) was significantly higher at early and late pregnancy compared with postpartum (all P < 0.05) and correlated with nicotine C-oxidation (all P < 0.001), suggesting CYP2A6 activity is induced during pregnancy. Nicotine 179-187 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 231-237 30087722-0 2018 Genetic Polymorphism of CYP2A6 and Its Relationship with Nicotine Metabolism in Male Bataknese Smokers Suffered from Lung Cancer in Indonesia. Nicotine 57-65 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 24-30 30087722-2 2018 AIM: This study aimed to analyse the relationship between CYP2A6 gene polymorphism with nicotine metabolism rates and lung cancer incidence among smokers of Batak ethnic group in Indonesia. Nicotine 88-96 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 58-64 30087722-10 2018 CONCLUSION: Among the Bataknese smokers studied, the CYP2A6*1B allele was found to be the most common allele and showed the highest rate of nicotine metabolism. Nicotine 140-148 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 53-59 28472521-5 2018 Results: These Key results involve genetic variants in the nicotinic receptor subunit gene CHRNA5, variants in the nicotine metabolism gene CYP2A6, and the nicotine metabolite ratio. Nicotine 115-123 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 140-146 29158210-9 2018 In conclusion, pregnancy-induced increases in nicotine metabolism start by 12 weeks gestation and continue as pregnancy progresses most likely due to induction of CYP2A6 and UGT2B10, resulting in potential reductions in the effectiveness of nicotine replacement therapies and an increase in metabolism of other CYP2A6 and UGT2B10 substrates during pregnancy. Nicotine 46-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 311-317 29158210-9 2018 In conclusion, pregnancy-induced increases in nicotine metabolism start by 12 weeks gestation and continue as pregnancy progresses most likely due to induction of CYP2A6 and UGT2B10, resulting in potential reductions in the effectiveness of nicotine replacement therapies and an increase in metabolism of other CYP2A6 and UGT2B10 substrates during pregnancy. Nicotine 241-249 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 163-169 29232328-0 2018 Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism. Nicotine 111-119 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 28032407-1 2018 Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Nicotine 80-88 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 28032407-1 2018 Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Nicotine 80-88 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 28290528-3 2018 CYP2A6, the primary hepatic nicotine metabolism gene, is robustly associated with cigarette consumption but other enzymes contribute to nicotine metabolism. Nicotine 28-36 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 28290528-3 2018 CYP2A6, the primary hepatic nicotine metabolism gene, is robustly associated with cigarette consumption but other enzymes contribute to nicotine metabolism. Nicotine 136-144 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 28290528-5 2018 The polymorphism rs2266780 (E308G) was associated with N-oxidation of both orally administered and ad libitum smoked nicotine (P<=3.3 x 10-5 controlling for CYP2A6 genotype). Nicotine 117-125 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 160-166 29232328-1 2018 OBJECTIVES: Smoking patterns and cessation rates vary widely across smokers and can be influenced by variation in rates of nicotine metabolism [i.e. cytochrome P450 2A6 (CYP2A6), enzyme activity]. Nicotine 123-131 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 149-168 29232328-1 2018 OBJECTIVES: Smoking patterns and cessation rates vary widely across smokers and can be influenced by variation in rates of nicotine metabolism [i.e. cytochrome P450 2A6 (CYP2A6), enzyme activity]. Nicotine 123-131 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 170-176 29232328-2 2018 There is high heritability of CYP2A6-mediated nicotine metabolism (60-80%) owing to known and unidentified genetic variation in the CYP2A6 gene. Nicotine 46-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 30-36 29232328-2 2018 There is high heritability of CYP2A6-mediated nicotine metabolism (60-80%) owing to known and unidentified genetic variation in the CYP2A6 gene. Nicotine 46-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 132-138 29232328-9 2018 Two pairs of novel SNPs were in high linkage disequilibrium, allowing us to establish five-SNP diplotypes that were associated with CYP2A6 enzyme activity (rate of nicotine metabolism) in-vitro in the liver bank and in-vivo among smokers. Nicotine 164-172 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 132-138 29232328-10 2018 CONCLUSION: The novel five-SNP diplotype may be useful to incorporate into CYP2A6 genotype models for personalized prediction of nicotine metabolism rate, cessation success, and response to pharmacotherapies. Nicotine 129-137 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 75-81 28856944-1 2017 The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Nicotine 91-99 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-41 29048184-1 2017 Nicotine is metabolized into cotinine and then into trans-3"-hydroxycotinine, mainly by cytochrome P450 2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-107 28556459-9 2017 In our in-vitro experiments we assessed the effect of caffeic acid, quercetin and p-coumaric acid on the rate of nicotine metabolism in human liver microsomes and cDNA-expressed human CYP2A6. Nicotine 113-121 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 184-190 29048184-7 2017 The hazard ratio of relapsing was estimated in multivariate Cox regression models including the sex and the nicotine metabolism determined by the phenotype or by CYP2A6 genotyping (rs1801272 and rs28399433). Nicotine 108-116 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 162-168 28181923-7 2017 RESULTS: The overall frequency of genetically reduced nicotine metabolizers, those with CYP2A6 decrease-of-function or loss-of-function alleles, was lower in the NP compared with the SW (P=0.0006). Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-94 28734893-2 2017 The CYP2A6 gene encodes the main enzyme responsible for nicotine metabolism. Nicotine 56-64 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 4-10 28734893-4 2017 Therefore, we evaluated the possible association between SNPs in CYP2A6 with cigarette smoking and nicotine addiction-related variables in Mexican mestizo smokers. Nicotine 99-107 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 28583088-10 2017 Finally, we found that liver-specific CHRNA4 transcription was highly correlated with genes involved in the nicotine metabolism, including CYP2A6, UGT2B7, and FMO3. Nicotine 108-116 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 139-145 28542511-4 2017 In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 17-36 28542511-4 2017 In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 28542511-4 2017 In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. Nicotine 192-200 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 17-36 28542511-4 2017 In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. Nicotine 192-200 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 28432340-4 2017 No association was observed in a sample of 3,245 nicotine-unexposed individuals from the same discovery cohort, consistent with the conclusion that the finding is related to CYP2A6 involvement in nicotine metabolism. Nicotine 196-204 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 174-180 27865452-1 2017 BACKGROUND: Variation in the CYP2A6 gene alters the rate of nicotine metabolic inactivation and is associated with smoking behaviors and cessation success rates. Nicotine 60-68 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 29-35 27865452-9 2017 CONCLUSIONS: Because the CYP2A6 effect was seen only in smokers, these data suggest that the rate of nicotine metabolism-and thus the concentration of nicotine presented to the brain over the course of nicotine addiction-shapes brain circuits that, among other functions, compute reward and impulsivity processes. Nicotine 101-109 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 27865452-9 2017 CONCLUSIONS: Because the CYP2A6 effect was seen only in smokers, these data suggest that the rate of nicotine metabolism-and thus the concentration of nicotine presented to the brain over the course of nicotine addiction-shapes brain circuits that, among other functions, compute reward and impulsivity processes. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 27865452-9 2017 CONCLUSIONS: Because the CYP2A6 effect was seen only in smokers, these data suggest that the rate of nicotine metabolism-and thus the concentration of nicotine presented to the brain over the course of nicotine addiction-shapes brain circuits that, among other functions, compute reward and impulsivity processes. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 28298240-1 2017 BACKGROUND: Cytochrome P450 2A5 (Cyp2a5), a mouse enzyme orthologous of human CYP2A6, catalyzes a number of toxicologically important reactions, including the metabolism of nicotine, aflatoxin B1, and several other xeno- and endobiotics. Nicotine 173-181 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 78-84 27815364-1 2017 Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke. Nicotine 90-98 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 27974382-0 2017 Functional Characterization of 34 CYP2A6 Allelic Variants by Assessment of Nicotine C-Oxidation and Coumarin 7-Hydroxylation Activities. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 34-40 27974382-1 2017 CYP2A6, a member of the cytochrome P450 (P450) family, is one of the enzymes responsible for the metabolism of therapeutic drugs and such tobacco components as nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and N-nitrosodiethylamine. Nicotine 160-168 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 27974382-3 2017 In this study, we conducted an in vitro analysis of 34 allelic variants of CYP2A6 using nicotine and coumarin as representative CYP2A6 substrates. Nicotine 88-96 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 75-81 27974382-3 2017 In this study, we conducted an in vitro analysis of 34 allelic variants of CYP2A6 using nicotine and coumarin as representative CYP2A6 substrates. Nicotine 88-96 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 128-134 27974382-4 2017 These variant CYP2A6 proteins were heterologously expressed in 293FT cells, and their enzymatic activities were assessed on the basis of nicotine C-oxidation and coumarin 7-hydroxylation activities. Nicotine 137-145 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 14-20 27974382-5 2017 Among the 34 CYP2A6 variants, CYP2A6.2, CYP2A6.5, CYP2A6.6, CYP2A6.10, CYP2A6.26, CYP2A6.36, and CYP2A6.37 exhibited no enzymatic activity, whereas 14 other variants exhibited markedly reduced activity toward both nicotine and coumarin. Nicotine 214-222 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 13-19 27815364-1 2017 Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke. Nicotine 90-98 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 20-26 27815364-5 2017 CYP2A6 enzyme activity was determined through measurement of cotinine formation from nicotine and 7-hydroxycoumarin formation from coumarin. Nicotine 85-93 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 27815364-15 2017 Overall, several independent and shared sources of variation in CYP2A6 activity in vitro have been identified, which could translate to variable hepatic clearance of nicotine. Nicotine 166-174 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 27035242-1 2016 OBJECTIVE: The rate of nicotine metabolism, determined primarily by CYP2A6 activity, influences tobacco dependence and smoking-induced disease risk. Nicotine 23-31 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 68-74 28101244-1 2016 Human cytochrome P450 (CYP) 2A6 participates in the metabolism of nicotine and precarcinogens, thus the deliberate inhibition of CYP2A6 may reduce cigarette consumption and therefore reduce the risk of developing the types of cancer associated with smoking. Nicotine 66-74 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 129-135 27488534-1 2016 Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant of smoking dose and, consequently, lung cancer risk. Nicotine 14-22 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 26-45 27488534-1 2016 Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant of smoking dose and, consequently, lung cancer risk. Nicotine 14-22 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 27488534-4 2016 CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine equivalents (a measure of nicotine uptake). Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 27488534-4 2016 CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine equivalents (a measure of nicotine uptake). Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 27599351-2 2016 In the current study, a pharmacokinetic-pharmacogenetic integrated approach is described, based on the development of a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for nicotine metabolite ratio assay in plasma and a real-time PCR analysis for fast genotyping of CYP2A6. Nicotine 189-197 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 283-289 27599351-6 2016 Overall, the findings of the current study demonstrate that the simultaneous assessment of nicotine metabolite ratio and CYP2A6 genotype from human blood samples is feasible and accurate and could be used in a smoking cessation program to optimize treatments and identify those smokers who inherit metabolically deficient CYP2A6 alleles. Nicotine 91-99 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 322-328 27338962-4 2016 Nicotine use disorders are associated with polymorphisms in a cluster of nicotinic acetylcholine receptors on chromosome 15q24, and mutations that reduce the enzymatic activity of CYP2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 180-186 27035242-3 2016 We studied nicotine disposition kinetics and metabolism by the CYP2A6 genotype and enzymatic activity, as measured by the nicotine metabolite ratio (NMR), in African American smokers. Nicotine 11-19 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 63-69 27035242-10 2016 CONCLUSION: CYP2A6 genotype, NMR, and nicotine pharmacokinetic data may inform studies of individual differences in smoking behavior and biomarkers of nicotine exposure. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 26069034-2 2016 Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. Nicotine 112-120 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 26851241-0 2016 Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. Nicotine 131-139 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-22 26541911-1 2016 INTRODUCTION: In very novice smokers, CYP2A6 genotypes that reduce nicotine metabolism to an intermediate rate may increase smoking risk, relative to both normal and slow rates. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 26541911-4 2016 Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 Diplotype Predicted Rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Nicotine 10-18 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 43-49 26541911-4 2016 Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 Diplotype Predicted Rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Nicotine 10-18 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 62-68 26541911-11 2016 IMPLICATIONS: This study supports our recent hypothesis that CYP2A6 diplotypes that encode intermediate nicotine metabolism rate are associated with enhanced pleasurable events following the initial smoking attempt, compared with diplotypes that encode either normal or slow metabolism. Nicotine 104-112 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 61-67 26014804-1 2015 BACKGROUND: The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3"-hydroxycotinine (3HC). Nicotine 70-78 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 51-57 26818358-1 2016 Genetic variation in cytochrome P450 2A6 (CYP2A6) gene is the primary contributor to the intraindividual and interindividual differences in nicotine metabolism and has been found to influence smoking intensity. Nicotine 140-148 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-40 26818358-1 2016 Genetic variation in cytochrome P450 2A6 (CYP2A6) gene is the primary contributor to the intraindividual and interindividual differences in nicotine metabolism and has been found to influence smoking intensity. Nicotine 140-148 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 42-48 25744963-1 2016 INTRODUCTION: The present study sought to identify time-dependent within-participant effects of CYP2A6 genotypes on smoking frequency and nicotine dependence in young smokers. Nicotine 138-146 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 25744963-2 2016 METHODS: Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 diplotype predicted rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Nicotine 19-27 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 52-58 25744963-2 2016 METHODS: Predicted nicotine metabolic rate based on CYP2A6 diplotypes (CYP2A6 diplotype predicted rate [CDPR]) was partitioned into Normal, Intermediate, and Slow categories using a metabolism metric. Nicotine 19-27 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 71-77 26648056-5 2016 Administering chemical inhibitors of CYP2A6 has been shown to slow down the elimination of nicotine with consequent reduction in number of cigarettes smoked. Nicotine 91-99 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 37-43 26272810-1 2015 UNLABELLED: The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine 16-24 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 26272810-1 2015 UNLABELLED: The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine 77-85 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 26272810-1 2015 UNLABELLED: The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine 77-85 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 26272810-1 2015 UNLABELLED: The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine 77-85 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 26407342-7 2015 The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 51-57 26100465-8 2015 In humans, nicotine is metabolized primarily by hepatic CYP2A6. Nicotine 11-19 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 56-62 26100465-11 2015 When CYP2A6 is substantially inhibited, nicotine clearance is delayed and nicotine withdrawal symptoms are attenuated. Nicotine 40-48 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 5-11 26100465-11 2015 When CYP2A6 is substantially inhibited, nicotine clearance is delayed and nicotine withdrawal symptoms are attenuated. Nicotine 74-82 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 5-11 26014804-2 2015 The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 80-86 25857233-1 2015 The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-29 25998026-15 2015 Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, methoxyflurane). Nicotine 133-141 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 26132489-1 2015 The Nicotine Metabolite Ratio (NMR, ratio of trans-3"-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 121-127 26132489-9 2015 We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Nicotine 49-57 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-39 25862079-1 2015 The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. Nicotine 98-106 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 4-10 25857233-1 2015 The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-37 25857233-1 2015 The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Nicotine 172-180 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-29 25857233-1 2015 The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Nicotine 172-180 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-37 25416559-2 2015 Previously, we found that CYP2A6, a nicotine/nitrosamine metabolism gene, was associated with lung cancer risk in European Americans, but smoking habits, lung cancer risk and CYP2A6 gene variants differ significantly between European and African ancestry populations. Nicotine 36-44 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 26-32 26060595-0 2015 CYP2A6 Polymorphisms May Strengthen Individualized Treatment for Nicotine Dependence. Nicotine 65-73 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 26370685-0 2015 EFFECT OF CYP2A6*4 GENETIC POLYMORPHISMS ON SMOKING BEHAVIORS AND NICOTINE DEPENDENCE IN A GENERAL POPULATION OF JAPANESE MEN. Nicotine 66-74 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 26370685-1 2015 OBJECTIVES: Nicotine in cigarettes is metabolized primarily by CYP2A6-catalyzed oxidation. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 63-69 26370685-3 2015 The aim of this study was to examine the effects of CYP2A6*4 genetic polymorphism on smoking behavior and nicotine dependence in a general population of Japanese men. Nicotine 106-114 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 52-58 26370685-11 2015 CONCLUSIONS: CYP2A6*4 genetic polymorphisms may not strongly affect smoking behavior but may possibly have an effect on nicotine dependence. Nicotine 120-128 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 13-19 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 34-40 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 34-40 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 26060595-5 2015 An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence. Nicotine 59-67 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 15-21 26060595-5 2015 An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 15-21 26060595-5 2015 An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 15-21 25655887-2 2015 Nicotine, the major psychoactive compound in cigarette smoke, is metabolized by a number of enzymes, including CYP2A6, CYP2B6, FMOs, and UGTs, among others. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 111-117 25655887-3 2015 Variation in the genes encoding these enzymes, in particular CYP2A6, can alter the rate of nicotine metabolism and smoking behaviors. Nicotine 91-99 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 61-67 26060595-1 2015 Each CYP2A6 gene variant metabolizes nicotine differently depending on its enzymatic activities. Nicotine 37-45 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 5-11 26060595-2 2015 The normal nicotine metabolizer CYP2A6(*)1A is associated with high scores of nicotine dependence (5-10) on the Fagerstrom Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Nicotine 11-19 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 32-38 26060595-2 2015 The normal nicotine metabolizer CYP2A6(*)1A is associated with high scores of nicotine dependence (5-10) on the Fagerstrom Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Nicotine 78-86 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 32-38 26060595-2 2015 The normal nicotine metabolizer CYP2A6(*)1A is associated with high scores of nicotine dependence (5-10) on the Fagerstrom Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Nicotine 132-140 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 32-38 26060595-2 2015 The normal nicotine metabolizer CYP2A6(*)1A is associated with high scores of nicotine dependence (5-10) on the Fagerstrom Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Nicotine 78-86 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 32-38 26060595-3 2015 Slow nicotine metabolizers (i.e., CYP2A6(*)1H, CYP2A6(*)4A, CYP2A6(*)9, and CYP2A6(*)12A) are associated with underrated nicotine metabolizing activity (50%-75%), linking them to low scores for nicotine dependence (0-4) on the FTND scale. Nicotine 5-13 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 34-40 25458499-1 2014 Inhibition of CYP2A6-mediated nicotine metabolism can reduce cigarette smoking. Nicotine 30-38 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 14-20 24859605-1 2014 Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the principal pathway by which active nicotine is removed from circulation. Nicotine 14-22 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 62-68 25446842-1 2014 The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. Nicotine 98-106 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 4-10 25220663-0 2014 Smilax China root extract detoxifies nicotine by reducing reactive oxygen species and inducing CYP2A6. Nicotine 37-45 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 95-101 25220663-7 2014 A significant amount of the conversion of nicotine to cotinine was observed in EESC pretreatment by CYP2A6 induction in HepG2 cells. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 100-106 25220663-8 2014 These results suggested that hepatic induction of CYP2A6 and ROS reduction by EESC activate nicotine metabolism and reduce cellular oxidative stress. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 50-56 24859605-1 2014 Metabolism of nicotine to inactive cotinine by hepatic enzyme CYP2A6 is the principal pathway by which active nicotine is removed from circulation. Nicotine 110-118 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 62-68 24859605-2 2014 We therefore hypothesized that inhibition of mouse CYP2A5, the ortolog of human CYP2A6, by methoxsalen (8-methoxypsoralen) alter dependence-related behaviors of nicotine in the mouse. Nicotine 161-169 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 80-86 24859605-11 2014 Combining CYP2A6 inhibitors with low dose nicotine replacement therapies may have a beneficial role in smoking cessation because it will decrease the drug elimination rate and maintain plasma and brain nicotine levels. Nicotine 202-210 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 24631364-0 2014 Binding free energies for nicotine analogs inhibiting cytochrome P450 2A6 by a combined use of molecular dynamics simulations and QM/MM-PBSA calculations. Nicotine 26-34 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 54-73 24983901-15 2014 The lack of nicotine metabolism in this model could be explained by the functional loss of CYP2A6 during chronic nicotine exposure. Nicotine 113-121 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 91-97 24631364-1 2014 Molecular dynamics (MD) simulations and hybrid quantum mechanical/molecular mechanical (QM/MM) calculations have been performed to explore the dynamic behaviors of cytochrome P450 2A6 (CYP2A6) binding with nicotine analogs (that are typical inhibitors) and to calculate their binding free energies in combination with Poisson-Boltzmann surface area (PBSA) calculations. Nicotine 206-214 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 164-183 24631364-1 2014 Molecular dynamics (MD) simulations and hybrid quantum mechanical/molecular mechanical (QM/MM) calculations have been performed to explore the dynamic behaviors of cytochrome P450 2A6 (CYP2A6) binding with nicotine analogs (that are typical inhibitors) and to calculate their binding free energies in combination with Poisson-Boltzmann surface area (PBSA) calculations. Nicotine 206-214 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 185-191 24527722-1 2014 Inhibition of human cytochrome P450 2A6 has been demonstrated to play an important role in nicotine metabolism and consequent smoking habits. Nicotine 91-99 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 20-39 24527722-7 2014 The chimeric system was also successfully used to demonstrate the inhibition of the electrochemical activity of the immobilized CYP2A6-FLD, toward both coumarin and nicotine substrates, by tranylcypromine, a potent and selective CYP2A6 inhibitor. Nicotine 165-173 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 128-134 24527722-7 2014 The chimeric system was also successfully used to demonstrate the inhibition of the electrochemical activity of the immobilized CYP2A6-FLD, toward both coumarin and nicotine substrates, by tranylcypromine, a potent and selective CYP2A6 inhibitor. Nicotine 165-173 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 229-235 24033696-0 2014 Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Nicotine 55-63 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 81-87 24448396-1 2014 The rates of nicotine metabolism differ widely, even after controlling for genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Nicotine 106-114 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 136-142 24045616-1 2014 Genome-wide significant associations with cigarettes per day (CPD) and risk for lung cancer and chronic obstructive pulmonary disease (COPD) were previously reported in a region of 19q13, including CYP2A6 (nicotine metabolism enzyme) and EGLN2 (hypoxia response). Nicotine 206-214 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 198-204 24033696-6 2014 MEASUREMENTS: Survival analysis was used to model time to relapse using nicotine metabolism derived from CYP2A6 genotype-based estimates. Nicotine 72-80 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 24033696-9 2014 Further, only the effect of nicotine replacement, and not bupropion, varies with CYP2A6-defined metabolic function. Nicotine 28-36 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 81-87 24033696-10 2014 The effect of nicotine replacement on continuous abstinence is moderated by the combined genetic risks from CYP2A6 and CHRNA5 (Wald = 7.44, d.f. Nicotine 14-22 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 108-114 25343290-1 2014 Cytochrome P450 2A6 (P450 2A6) is the major enzyme responsible for the oxidation of coumarin, nicotine, and tobacco-specific nitrosamines in human liver. Nicotine 94-102 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 23933970-4 2013 Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 117-123 23933970-4 2013 Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. Nicotine 160-168 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 117-123 23936477-1 2013 BACKGROUND: CYP2A6 metabolizes nicotine to its primary metabolite cotinine and also mediates the metabolism of cotinine to trans-3"-hydroxycotinine (3HC). Nicotine 31-39 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 23674838-1 2013 INTRODUCTION: The nicotine metabolite ratio (NMR), the ratio of trans-3"-hydroxycotinine (3-HC) to cotinine, has been used as a biomarker of the rate of CYP2A6-mediated nicotine metabolism. Nicotine 18-26 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 153-159 23674838-1 2013 INTRODUCTION: The nicotine metabolite ratio (NMR), the ratio of trans-3"-hydroxycotinine (3-HC) to cotinine, has been used as a biomarker of the rate of CYP2A6-mediated nicotine metabolism. Nicotine 169-177 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 153-159 23714690-1 2013 The formation of cotinine, the main proximate metabolite and a biomarker of nicotine exposure, is mediated primarily by cytochrome P450 (CYP)2A6. Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 137-144 23936477-10 2013 This study demonstrates that NMR is not altered by differences in the rate of 3HC glucuronidation, providing further support that NMR is a reliable indicator of CYP2A6 mediated nicotine metabolism. Nicotine 177-185 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 161-167 24192532-0 2013 The contribution of common UGT2B10 and CYP2A6 alleles to variation in nicotine glucuronidation among European Americans. Nicotine 70-78 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 24192532-8 2013 CONCLUSION: CYP2A6 and UGT2B10 genotype explain 53% of the variance in oral nicotine glucuronidation in this sample. Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 24192532-9 2013 CYP2A6 and UGT2B10 genetic variants are also significantly associated with undeuterated (D0) nicotine glucuronidation in individuals smoking ad libitum. Nicotine 93-101 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 24260284-2 2013 Using CYP2A6 genotype as a covariate, we find that a non-coding polymorphism in CYP2B6 previously associated with smoking cessation (rs8109525) is also significantly associated with nicotine metabolism. Nicotine 182-190 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 23936477-2 2013 The ratio of 3HC to cotinine (the "nicotine metabolite ratio", NMR) is an in vivo marker for the rate of CYP2A6 mediated nicotine metabolism, and total nicotine clearance, and has been associated with differences in numerous smoking behaviors. Nicotine 35-43 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 23936477-2 2013 The ratio of 3HC to cotinine (the "nicotine metabolite ratio", NMR) is an in vivo marker for the rate of CYP2A6 mediated nicotine metabolism, and total nicotine clearance, and has been associated with differences in numerous smoking behaviors. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 23936477-2 2013 The ratio of 3HC to cotinine (the "nicotine metabolite ratio", NMR) is an in vivo marker for the rate of CYP2A6 mediated nicotine metabolism, and total nicotine clearance, and has been associated with differences in numerous smoking behaviors. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 23530019-7 2013 In humans, cytochrome P450 2A6 metabolizes nicotine to cotinine, and CYP2A-like activity and protein have been reported in some birds. Nicotine 43-51 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 11-30 23528144-1 2013 Functional CYP2A6 genetic variation partially determines nicotine metabolism. Nicotine 57-65 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 11-17 22934830-3 2013 2. qRT-PCR studies demonstrated significant constitutive mRNA expression of CYP2A-isoenzymes in PBL isolated from male and female rats which further increases significantly after pretreatment with nicotine or 3-methylcholanthrene (MC) indicating responsiveness of CYP2A-isoenzymes in PBL. Nicotine 197-205 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 76-81 23371292-0 2013 The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 104-110 23462429-0 2013 CYP2A6 slow nicotine metabolism is associated with increased quitting by adolescent smokers. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 23462429-1 2013 Variation in the CYP2A6 gene, which decreases the rate of nicotine metabolic inactivation, is associated with higher adult smoking cessation rates during clinical trials. Nicotine 58-66 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 17-23 22934830-3 2013 2. qRT-PCR studies demonstrated significant constitutive mRNA expression of CYP2A-isoenzymes in PBL isolated from male and female rats which further increases significantly after pretreatment with nicotine or 3-methylcholanthrene (MC) indicating responsiveness of CYP2A-isoenzymes in PBL. Nicotine 197-205 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 264-269 23303461-1 2013 The fundamental reaction mechanism of cytochrome P450 2A6 (CYP2A6)-catalyzed N-methylhydroxylation of (S)-(-)-nicotine and the free energy profile have been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical (QM/MM) reaction-coordinate calculations. Nicotine 102-118 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-57 23303461-1 2013 The fundamental reaction mechanism of cytochrome P450 2A6 (CYP2A6)-catalyzed N-methylhydroxylation of (S)-(-)-nicotine and the free energy profile have been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical (QM/MM) reaction-coordinate calculations. Nicotine 102-118 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 59-65 23292114-1 2013 A synonymous variant in the first exon of CYP2A6, rs1137115 (51G>A), defines the common reference allele CYP2A6*1A, and is associated with lower mRNA expression and slower in-vivo nicotine metabolism. Nicotine 183-191 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 108-114 23112005-1 2013 CYP 2A6 is a human enzyme that metabolizes many xenobiotics including coumarin, indole, nicotine and carcinogenic nitrosamines. Nicotine 88-96 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-7 23203414-1 2013 Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco-specific carcinogens (such as N-nitrosamines). Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 23292114-1 2013 A synonymous variant in the first exon of CYP2A6, rs1137115 (51G>A), defines the common reference allele CYP2A6*1A, and is associated with lower mRNA expression and slower in-vivo nicotine metabolism. Nicotine 183-191 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 42-48 23211429-3 2013 METHODS: A genetic model of CYP2A6 function is used as a covariate to reveal functional polymorphism in FMO3 that indirectly influences the ratio of deuterated nicotine metabolized to cotinine following oral administration. Nicotine 160-168 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-34 23211429-7 2013 Cross-validation demonstrates calculated FMO3 haplotype parameters to be robust and significantly improve the predictive nicotine metabolism model over CYP2A6 genotype alone. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 152-158 23211429-8 2013 Functional classes of FMO3 haplotypes, as determined by their influence on nicotine metabolism to cotinine, are also significantly associated with cigarettes per day in nicotine-dependent European Americans (n=1025, P=0.04), and significantly interact (P=0.016) with CYP2A6 genotype to predict cigarettes per day. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 267-273 23211429-8 2013 Functional classes of FMO3 haplotypes, as determined by their influence on nicotine metabolism to cotinine, are also significantly associated with cigarettes per day in nicotine-dependent European Americans (n=1025, P=0.04), and significantly interact (P=0.016) with CYP2A6 genotype to predict cigarettes per day. Nicotine 169-177 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 267-273 23049750-5 2012 Imputation of the CYP2A6 locus revealed that haplotypes underlying the CNP and the SNP corresponded to classical, functional alleles of CYP2A6 gene that regulate nicotine metabolism and explained 2% of the phenotypic variance of CPD (ANOVA F-test P=9.5 x 10(-52)). Nicotine 162-170 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 18-24 23027621-1 2013 Nicotine, the psychoactive ingredient in tobacco, is metabolically inactivated by CYP2A6 to cotinine. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 82-88 23027621-7 2013 Smokers, smokeless tobacco users and iqmik users with lower CYP2A6 activity had lower urinary total nicotine equivalents (TNE) and (methylnitrosamino)-1-(3)pyridyl-1-butanol (NNAL) levels (a biomarker of TSNA exposure). Nicotine 100-108 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 60-66 23821941-8 2013 Key role in the metabolism of nicotine is played by cytochrome P450 oxidases (mainly CYP2A6). Nicotine 30-38 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 85-91 22498344-0 2012 An LC-MS/MS method for concurrent determination of nicotine metabolites and the role of CYP2A6 in nicotine metabolite-mediated oxidative stress in SVGA astrocytes. Nicotine 98-106 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-94 22498344-1 2012 BACKGROUND: Nicotine is known to generate oxidative stress through cytochrome P450 2A6 (CYP2A6)-mediated metabolism in the liver and other organs, including macrophages. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 67-86 22498344-1 2012 BACKGROUND: Nicotine is known to generate oxidative stress through cytochrome P450 2A6 (CYP2A6)-mediated metabolism in the liver and other organs, including macrophages. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-94 22498344-2 2012 This study has been designed to examine the role of CYP2A6 in nicotine metabolism and oxidative stress in SVGA cells, an immortalized human astrocyte cell line. Nicotine 62-70 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 52-58 22498344-6 2012 RESULTS: Nicotine significantly upregulated mRNA and protein expression of the most abundantly expressed CYPs in SVGA astrocytes, CYP2A6 and CYP1A1. Nicotine 9-17 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 130-136 22498344-10 2012 Nicotine metabolism and ROS formation by CYP2A6 were further confirmed by using tryptamine, a selective inhibitor of CYP2A6, which significantly lowered the levels of cotinine and NNK and inhibited ROS formation. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 41-47 22498344-10 2012 Nicotine metabolism and ROS formation by CYP2A6 were further confirmed by using tryptamine, a selective inhibitor of CYP2A6, which significantly lowered the levels of cotinine and NNK and inhibited ROS formation. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 117-123 22498344-11 2012 CONCLUSIONS: CYP2A6 plays a key role in nicotine metabolism and oxidative stress in astrocytes, and this has implications in nicotine-associated brain toxicity. Nicotine 40-48 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 13-19 22498344-11 2012 CONCLUSIONS: CYP2A6 plays a key role in nicotine metabolism and oxidative stress in astrocytes, and this has implications in nicotine-associated brain toxicity. Nicotine 125-133 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 13-19 22700965-0 2012 Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone binding and access channel in human cytochrome P450 2A6 and 2A13 enzymes. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-124 22700965-3 2012 X-ray structures of nicotine complexes with CYP2A13 (2.5 A) and CYP2A6 (2.3 A) yield a structural rationale for the preferential binding of nicotine to CYP2A13. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 22700965-3 2012 X-ray structures of nicotine complexes with CYP2A13 (2.5 A) and CYP2A6 (2.3 A) yield a structural rationale for the preferential binding of nicotine to CYP2A13. Nicotine 140-148 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 22676413-0 2012 Cytochrome P450-catalyzed degradation of nicotine: fundamental parameters determining hydroxylation by cytochrome P450 2A6 at the 5"-carbon or the n-methyl carbon. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 103-122 22552800-1 2012 BACKGROUND: The nicotine metabolite ratio (NMR or 3-hydroxycotinine/cotinine) has been used to phenotype CYP2A6-mediated nicotine metabolism. Nicotine 16-24 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 22552800-1 2012 BACKGROUND: The nicotine metabolite ratio (NMR or 3-hydroxycotinine/cotinine) has been used to phenotype CYP2A6-mediated nicotine metabolism. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 22486895-1 2012 Nicotine is the primary addictive agent in tobacco products and is metabolized in humans by CYP2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 22486895-3 2012 The extrahepatic enzyme, CYP2A13 (94% identical to CYP2A6) also catalyzes the metabolism of nicotine, but is most noted for its role in the metabolic activation of the tobacco specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 51-57 22706231-6 2012 The two most relevant substrates for CYP2A6 are coumarin and nicotine. Nicotine 61-69 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 37-43 22706231-8 2012 Approximately 80% of a nicotine dose is eliminated by CYP2A6, and there is a clear link between CYP2A6 genotypes, smoking behavior, and lung cancer risk. Nicotine 23-31 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 54-60 22706231-8 2012 Approximately 80% of a nicotine dose is eliminated by CYP2A6, and there is a clear link between CYP2A6 genotypes, smoking behavior, and lung cancer risk. Nicotine 23-31 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 22569203-0 2012 CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people. Nicotine 61-69 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 22569203-2 2012 Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, have not been characterized in AN and may contribute toward the increased risk. Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 18-24 22569203-6 2012 Nicotine metabolism [as measured by the plasma and urinary ratio of metabolites trans-3"-hydroxycotinine to cotinine (3HC/COT)] was significantly associated with CYP2A6 (P<0.001), but not CYP2B6 genotype (P=0.95) when controlling for known covariates. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 162-168 22569203-8 2012 CONCLUSION: Yupik AN people have a unique CYP2A6 genetic profile that associated strongly with in-vivo nicotine metabolism. Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 42-48 22569203-9 2012 More rapid CYP2A6-mediated nicotine and nitrosamine metabolism in the Yupik people may modulate the risk of tobacco-related diseases. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 11-17 22218454-1 2012 RATIONALE: Certain compounds that nonselectively inhibit a prominent human nicotine-metabolizing enzyme (i.e., human cytochrome P-450 2A6, hCYP 2A6) showed inhibition of smoking in humans. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 117-137 22218454-1 2012 RATIONALE: Certain compounds that nonselectively inhibit a prominent human nicotine-metabolizing enzyme (i.e., human cytochrome P-450 2A6, hCYP 2A6) showed inhibition of smoking in humans. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 139-148 22218454-2 2012 However, a comprehensive examination of hCYP 2A6 inhibitors to decrease nicotine self-administration in rats has not been reported. Nicotine 72-80 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 40-48 22342802-2 2012 Nicotine metabolism, mediated by the enzyme CYP2A6, also influences smoking behavior. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 44-50 22160797-8 2012 Moreover, CYP2A6 poor metabolizer genotypes were associated with slower nicotine metabolism. Nicotine 72-80 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 22382327-1 2012 Cytochrome P450 2A6 (CYP2A6) catalyzes important metabolic reactions of many xenobiotic compounds, including coumarin, nicotine, cotinine, and clinical drugs. Nicotine 119-127 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 22382327-1 2012 Cytochrome P450 2A6 (CYP2A6) catalyzes important metabolic reactions of many xenobiotic compounds, including coumarin, nicotine, cotinine, and clinical drugs. Nicotine 119-127 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 22382327-9 2012 In the case of nicotine 5-oxidation, the CYP2A6*19 variant exhibited an increased K(m) value, whereas CYP2A6*18 and *35 showed much greater decreases in k(cat) values. Nicotine 15-23 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 41-47 22382327-9 2012 In the case of nicotine 5-oxidation, the CYP2A6*19 variant exhibited an increased K(m) value, whereas CYP2A6*18 and *35 showed much greater decreases in k(cat) values. Nicotine 15-23 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 102-108 23049750-5 2012 Imputation of the CYP2A6 locus revealed that haplotypes underlying the CNP and the SNP corresponded to classical, functional alleles of CYP2A6 gene that regulate nicotine metabolism and explained 2% of the phenotypic variance of CPD (ANOVA F-test P=9.5 x 10(-52)). Nicotine 162-170 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 136-142 21513309-1 2011 A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(-)-nicotine, demonstrating that the dominant molecular species of (S)-(-)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SR(t) and SR(c)), despite the fact that the protonated state is dominant for the free ligand in solution. Nicotine 101-117 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 57-76 21964962-5 2011 Subjects were genotyped for CYP2A6 and classified, according to genotype, into normal, intermediate, slow, or poor nicotine metabolizers based on prior knowledge of CYP2A6 allele associations with nicotine C-oxidation rate. Nicotine 197-205 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 165-171 21747048-1 2011 Genetic variations in the CYP2A6 nicotine metabolic gene and the CHRNA5-CHRNA3-CHRNB4 (CHRNA5-A3-B4) nicotinic gene cluster have been independently associated with lung cancer. Nicotine 33-41 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 26-32 21747048-5 2011 Cigarette consumption (P < .001) and nicotine dependence (P = .036) were the highest in the combined CYP2A6 normal metabolizers and CHRNA5-A3-B4 AA (tag single-nucleotide polymorphism rs1051730 G>A) risk group. Nicotine 40-48 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 104-110 21747048-7 2011 Variation in CYP2A6 and CHRNA5-A3-B4 was independently and additively associated with increased cigarette consumption, nicotine dependence, and lung cancer risk. Nicotine 119-127 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 13-19 22019468-1 2011 The human CYP2A6 enzyme metabolises several xenobiotics including nicotine, the addictive component in tobacco. Nicotine 66-74 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 21597399-0 2011 The contribution of common CYP2A6 alleles to variation in nicotine metabolism among European-Americans. Nicotine 58-66 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 21597399-1 2011 OBJECTIVE: To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism. Nicotine 100-108 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 44-63 21597399-1 2011 OBJECTIVE: To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism. Nicotine 100-108 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 21597399-1 2011 OBJECTIVE: To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism. Nicotine 199-207 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 44-63 21597399-1 2011 OBJECTIVE: To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism. Nicotine 199-207 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 21597399-8 2011 CONCLUSION: Among European-Americans, seven polymorphisms in the CYP2A6 gene explain the majority of variability in the metabolism of nicotine to cotinine after oral administration. Nicotine 134-142 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 21597399-9 2011 Parameters determined from this in-vivo experiment can be used to predict nicotine metabolism based on CYP2A6 genotype. Nicotine 74-82 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 103-109 21513309-1 2011 A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(-)-nicotine, demonstrating that the dominant molecular species of (S)-(-)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SR(t) and SR(c)), despite the fact that the protonated state is dominant for the free ligand in solution. Nicotine 101-117 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 78-84 21513309-1 2011 A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(-)-nicotine, demonstrating that the dominant molecular species of (S)-(-)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SR(t) and SR(c)), despite the fact that the protonated state is dominant for the free ligand in solution. Nicotine 101-117 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 192-198 21513309-1 2011 A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(-)-nicotine, demonstrating that the dominant molecular species of (S)-(-)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SR(t) and SR(c)), despite the fact that the protonated state is dominant for the free ligand in solution. Nicotine 172-188 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 57-76 21513309-1 2011 A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(-)-nicotine, demonstrating that the dominant molecular species of (S)-(-)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SR(t) and SR(c)), despite the fact that the protonated state is dominant for the free ligand in solution. Nicotine 172-188 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 78-84 21513309-1 2011 A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(-)-nicotine, demonstrating that the dominant molecular species of (S)-(-)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SR(t) and SR(c)), despite the fact that the protonated state is dominant for the free ligand in solution. Nicotine 172-188 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 192-198 21513309-2 2011 The computational results reveal that the dominant pathway of nicotine metabolism in CYP2A6 is through nicotine free base oxidation. Nicotine 62-70 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 85-91 21513309-2 2011 The computational results reveal that the dominant pathway of nicotine metabolism in CYP2A6 is through nicotine free base oxidation. Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 85-91 21513309-3 2011 Further, first-principles quantum mechanical/molecular mechanical free energy (QM/MM-FE) calculations were carried out to uncover the detailed reaction pathways for the CYP2A6-catalyzed nicotine 5"-hydroxylation reaction. Nicotine 186-194 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 169-175 21513309-5 2011 CYP2A6-catalyzed (S)-(-)-nicotine 5"-hydroxylation consists of two reaction steps, that is, the hydrogen transfer from the 5"-position of (S)-(-)-nicotine to the oxygen of Cpd I (the H-transfer step), followed by the recombination of the (S)-(-)-nicotine moiety with the iron-bound hydroxyl group to generate the 5"-hydroxynicotine product (the O-rebound step). Nicotine 17-33 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 21513309-5 2011 CYP2A6-catalyzed (S)-(-)-nicotine 5"-hydroxylation consists of two reaction steps, that is, the hydrogen transfer from the 5"-position of (S)-(-)-nicotine to the oxygen of Cpd I (the H-transfer step), followed by the recombination of the (S)-(-)-nicotine moiety with the iron-bound hydroxyl group to generate the 5"-hydroxynicotine product (the O-rebound step). Nicotine 138-154 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 21513309-5 2011 CYP2A6-catalyzed (S)-(-)-nicotine 5"-hydroxylation consists of two reaction steps, that is, the hydrogen transfer from the 5"-position of (S)-(-)-nicotine to the oxygen of Cpd I (the H-transfer step), followed by the recombination of the (S)-(-)-nicotine moiety with the iron-bound hydroxyl group to generate the 5"-hydroxynicotine product (the O-rebound step). Nicotine 138-154 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 21149643-4 2011 The polymorphic CYP2A6 has a role in nicotine metabolism and smoking behavior. Nicotine 37-45 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-22 21443033-0 2011 Relationship between CYP2A6 genetic polymorphism, as a marker of nicotine metabolism, and ulcerative colitis. Nicotine 65-73 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 21443033-4 2011 Nicotine is metabolized by the enzyme CYP2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 21443033-5 2011 Subjects who are homozygotes for CYP2A6*4 gene polymorphism are poor nicotine metabolizers, while homozygotes for CYP2A6*1A polymorphism are extensive metabolizers. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-39 20887713-1 2011 Human CYP2A6 is responsible for the metabolism of nicotine and coumarin as well as the metabolic activation of tobacco-related nitrosamines. Nicotine 50-58 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 21266057-6 2011 Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Nicotine 148-156 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 110-116 20717551-2 2010 Members of the population were genotyped for the nicotine-metabolizing enzyme cytochrome P450 2A6 (CYP2A6). Nicotine 49-57 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 78-97 21919071-6 2011 However, individual variability of CYP2A6 allele,in which nicotine is catalyzed to cotinine, affects the level of urinary cotinine. Nicotine 58-66 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 35-41 21919071-7 2011 Approximately 20% of Japanese subjects have homozygotes or heterozygotes of the CYP2A6*4 allele, which has impaired nicotine metabolism and subsequently may underestimate the actual exposure to SHS. Nicotine 116-124 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 80-86 22046326-8 2011 Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1). Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 108-114 20438369-0 2010 Association between nicotine metabolism and CYP2A6*1 and CYP2A6*4 genotypes in an Iranian population. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 44-50 20438369-0 2010 Association between nicotine metabolism and CYP2A6*1 and CYP2A6*4 genotypes in an Iranian population. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 57-63 20438369-2 2010 Among this family, CYP2A6 is one of the most important enzymes for metabolism of nicotine. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 19-25 20438369-3 2010 In this study, the linkage of CYP2A6*1 and CYP2A6*4 genotypes with nicotine metabolism was investigated. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 30-36 20438369-3 2010 In this study, the linkage of CYP2A6*1 and CYP2A6*4 genotypes with nicotine metabolism was investigated. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 43-49 20438369-8 2010 Cotinine formation from nicotine has individual and ethnic variability that correlated with the level of CYP2A6 expression. Nicotine 24-32 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 20717551-2 2010 Members of the population were genotyped for the nicotine-metabolizing enzyme cytochrome P450 2A6 (CYP2A6). Nicotine 49-57 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 99-105 20717551-4 2010 Plasma levels of 3"-hydroxycotinine and urinary levels of nicotine and 3"-hydroxycotinine were dependent on the CYP2A6 phenotype group, which was estimated from the CYP2A6 genotypes of the subjects, including those with whole gene deletion. Nicotine 58-66 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 112-118 20717551-4 2010 Plasma levels of 3"-hydroxycotinine and urinary levels of nicotine and 3"-hydroxycotinine were dependent on the CYP2A6 phenotype group, which was estimated from the CYP2A6 genotypes of the subjects, including those with whole gene deletion. Nicotine 58-66 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 165-171 20307138-7 2010 A weak correlation between CYP2B6 and nicotine C-oxidation activity was observed, which was abrogated when controlling for CYP2A6 protein levels. Nicotine 38-46 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 123-129 20012030-4 2010 RESULTS: Liver samples with variant CYP2A6 alleles had significantly lower CYP2A6 protein expression, nicotine C-oxidation activity, and affinity for nicotine. Nicotine 102-110 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 36-42 20012030-4 2010 RESULTS: Liver samples with variant CYP2A6 alleles had significantly lower CYP2A6 protein expression, nicotine C-oxidation activity, and affinity for nicotine. Nicotine 150-158 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 36-42 19959692-2 2009 Further, variability in CYP2A6, the enzyme that mediates formation of COT from nicotine and its metabolism to trans-3"-hydroxycotinine (3HC), may limit the usefulness of COT. Nicotine 79-87 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 24-30 20136358-1 2010 AIMS: Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing nicotine and nitrosamine precarcinogens. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-25 20136358-1 2010 AIMS: Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing nicotine and nitrosamine precarcinogens. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 20136358-8 2010 CONCLUSION: As new variants are discovered, the relationships between CYP2A6 genotype, nicotine metabolism, smoking behaviors and tobacco-related cancer risk will be further clarified. Nicotine 87-95 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 70-76 19702528-4 2009 Because CYP2A6 is responsible for 70-80% of the initial metabolism of nicotine, CYP2A6 has been proposed to be a novel target for smoking cessation. Nicotine 70-78 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 8-14 21784037-0 2009 The influence of CYP2A6 polymorphisms and cadmium on nicotine metabolism in Thai population. Nicotine 53-61 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 17-23 21784037-1 2009 We investigated the influence of genetic, cadmium exposure and smoking status, on cytochrome P450-mediated nicotine metabolism (CYP2A6) in 182 Thai subjects after receiving 2mg of nicotine gum chewing for 30min. Nicotine 107-115 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 128-134 19702528-4 2009 Because CYP2A6 is responsible for 70-80% of the initial metabolism of nicotine, CYP2A6 has been proposed to be a novel target for smoking cessation. Nicotine 70-78 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 80-86 19365400-1 2009 Cytochrome P450 2A6 (CYP2A6) is the primary human enzyme involved in nicotine metabolism. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 19090569-0 2009 Conceptual DFT properties-based 3D QSAR: analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme. Nicotine 71-79 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 93-99 19365400-1 2009 Cytochrome P450 2A6 (CYP2A6) is the primary human enzyme involved in nicotine metabolism. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 19365400-7 2009 In vitro, CYP2A6.35 had decreased nicotine C-oxidation activity and thermal stability. Nicotine 34-42 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 17923852-0 2008 Identification of inhibitors of the nicotine metabolising CYP2A6 enzyme--an in silico approach. Nicotine 36-44 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 58-64 19300303-5 2009 DNA was genotyped to confirm zygosity and for variation in the gene for the primary nicotine metabolic enzyme, CYP2A6 (variants genotyped: *1B, *1 x 2, *2, *4, *9, *12). Nicotine 84-92 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 111-117 19793020-1 2009 The nicotine metabolism of CYP2A6 (CYP2A6*1A,*1B, and *1C), and the cholecystokinin (CCK; which modulates the release of dopamine) and CCK-A receptor gene and personality traits for NEO-FFI, was investigated for the mechanism for elucidation of the smoking behavior in Japanese populations. Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 19793020-1 2009 The nicotine metabolism of CYP2A6 (CYP2A6*1A,*1B, and *1C), and the cholecystokinin (CCK; which modulates the release of dopamine) and CCK-A receptor gene and personality traits for NEO-FFI, was investigated for the mechanism for elucidation of the smoking behavior in Japanese populations. Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 35-41 19184652-6 2009 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. Nicotine 99-107 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 56-62 19184652-6 2009 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. Nicotine 168-176 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 56-62 19184652-7 2009 Thus, special attention will be given to CYP2A6, because slower nicotine metabolism requires less frequent self-administration, and accordingly influences smoking behaviors. Nicotine 64-72 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 41-47 18976031-1 2008 BACKGROUND: Genetic polymorphism of CYP2A6 gene is a major causal factor in the large interindividual differences in nicotine metabolism. Nicotine 117-125 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 36-42 19434638-2 2009 These compounds were tested as inhibitors of CYP2A6 and CYP2A13--two cytochrome P450 enzymes present in the respiratory tract--with a view to preventing the formation of carcinogenic metabolites of nicotine and inhibiting the metabolism of fragrances. Nicotine 198-206 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 45-51 19279561-1 2009 Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 19279561-1 2009 Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 19279561-1 2009 Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. Nicotine 51-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 19279561-1 2009 Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. Nicotine 51-54 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 19793020-2 2009 The frequency of the CYP2A6*4C allele, which is a whole deleted allele of the human CYP2A6 gene, was higher, whereas that of CYP2A6*1A/*1B heterozygotes with higher nicotine metabolism activity was lower in nonsmokers than in smokers. Nicotine 165-173 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 19793020-2 2009 The frequency of the CYP2A6*4C allele, which is a whole deleted allele of the human CYP2A6 gene, was higher, whereas that of CYP2A6*1A/*1B heterozygotes with higher nicotine metabolism activity was lower in nonsmokers than in smokers. Nicotine 165-173 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 19793020-2 2009 The frequency of the CYP2A6*4C allele, which is a whole deleted allele of the human CYP2A6 gene, was higher, whereas that of CYP2A6*1A/*1B heterozygotes with higher nicotine metabolism activity was lower in nonsmokers than in smokers. Nicotine 165-173 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 19029401-2 2008 Nicotine metabolism by cytochrome P450 2A6 (CYP2A6) varies across ethnicity/race and is hypothesized to affect smoking behavior. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 23-42 19029401-2 2008 Nicotine metabolism by cytochrome P450 2A6 (CYP2A6) varies across ethnicity/race and is hypothesized to affect smoking behavior. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 44-50 19029401-3 2008 We investigated whether higher CYP2A6 activity results in the smoker extracting more nicotine (adjusting for cigarettes per day) and being exposed to higher levels of tobacco-specific nitrosamine [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] and pyrene, a representative polycyclic aromatic hydrocarbon. Nicotine 85-93 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-37 19029401-5 2008 We assessed CYP2A6 activity by nicotine metabolite ratio (total trans-3-hydroxycotinine/total cotinine) and caffeine metabolite ratio (1,7-dimethyl uric acid/1,7-dimethylxanthine) in 12 h urine. Nicotine 31-39 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 19029401-9 2008 Nicotine equivalents and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol increased with CYP2A6 activity, indicating that smokers with greater nicotine metabolism smoke more extensively and have a higher internal NNK dose. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 19029401-9 2008 Nicotine equivalents and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol increased with CYP2A6 activity, indicating that smokers with greater nicotine metabolism smoke more extensively and have a higher internal NNK dose. Nicotine 146-154 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 18779312-2 2008 A number of compounds, including nicotine, cotinine, and aflatoxin B(1), are metabolites of the 94% identical CYP2A13 and CYP2A6 enzymes but at different rates. Nicotine 33-41 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 122-128 17923852-2 2008 Nicotine is eliminated by metabolism through the cytochrome P450 2A6 (CYP2A6) enzyme in liver. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 49-68 17923852-2 2008 Nicotine is eliminated by metabolism through the cytochrome P450 2A6 (CYP2A6) enzyme in liver. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 70-76 17923852-11 2008 This compound can be used as a lead in the design of CYP2A6 inhibitor drugs to combat nicotine addiction. Nicotine 86-94 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 53-59 18360915-0 2008 Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. Nicotine 52-60 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 22-28 18559554-1 2008 BACKGROUND: The ratio of two nicotine metabolites, cotinine and trans-3"-hydroxycotinine (3-HC), has been validated as a method of phenotyping the activity of the liver enzyme cytochrome P450 (CYP) 2A6 and, thus, the rate of nicotine metabolism. Nicotine 29-37 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 176-201 18559554-1 2008 BACKGROUND: The ratio of two nicotine metabolites, cotinine and trans-3"-hydroxycotinine (3-HC), has been validated as a method of phenotyping the activity of the liver enzyme cytochrome P450 (CYP) 2A6 and, thus, the rate of nicotine metabolism. Nicotine 225-233 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 176-201 18360915-1 2008 Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens. Nicotine 110-118 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 18360915-1 2008 Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens. Nicotine 110-118 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 17522595-0 2008 Identification of novel CYP2A6*1B variants: the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism. Nicotine 99-107 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 24-30 18065502-0 2008 Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice. Nicotine 65-73 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 18065502-8 2008 Selegiline dose- and time-dependently inhibited nicotine metabolism by CYP2A6 (K(i) = 15.6 +/- 2.7 muM; k(inact) = 0.34 +/- 0.04 min(-1)), and the inhibition was irreversible in the presence of NADPH, indicating that it is a mechanism-based inhibitor of CYP2A6. Nicotine 48-56 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 71-77 18065502-8 2008 Selegiline dose- and time-dependently inhibited nicotine metabolism by CYP2A6 (K(i) = 15.6 +/- 2.7 muM; k(inact) = 0.34 +/- 0.04 min(-1)), and the inhibition was irreversible in the presence of NADPH, indicating that it is a mechanism-based inhibitor of CYP2A6. Nicotine 48-56 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 254-260 17978169-1 2008 Human cytochrome P450 2A6 (CYP2A6) metabolizes various clinically relevant compounds, including nicotine- and tobacco-specific procarcinogens; however, transcriptional regulation of this gene is poorly understood. Nicotine 96-104 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 17522595-0 2008 Identification of novel CYP2A6*1B variants: the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism. Nicotine 99-107 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 48-54 17522595-1 2008 Cytochrome P450 2A6 (CYP2A6) is the human enzyme responsible for the majority of nicotine"s metabolism. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 17522595-1 2008 Cytochrome P450 2A6 (CYP2A6) is the human enzyme responsible for the majority of nicotine"s metabolism. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 17522595-2 2008 CYP2A6 genetic variants contribute to the interindividual and interethnic variation in nicotine metabolism. Nicotine 87-95 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 17522595-3 2008 We examined the association between the CYP2A6*1B variant and nicotine"s in vivo metabolism. Nicotine 62-70 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 40-46 17522595-8 2008 We report evidence that CYP2A6*1B genotype is associated with faster nicotine clearance in vivo, which will be important to future CYP2A6 genotype association studies. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 24-30 17522595-8 2008 We report evidence that CYP2A6*1B genotype is associated with faster nicotine clearance in vivo, which will be important to future CYP2A6 genotype association studies. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 131-137 17620343-3 2007 A similar inhibition pattern was observed in nicotine C oxidation, which is also one of the prototype reactions of CYP2A6. Nicotine 45-53 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 115-121 18216723-1 2008 OBJECTIVES: CYP2A6 is the main enzyme involved in nicotine metabolism in humans. Nicotine 50-58 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 18216723-6 2008 In vitro, CYP2A6.23 had greatly reduced activity toward nicotine C-oxidation similar to CYP2A6.17, as well as reduced coumarin 7-hydroxylation. Nicotine 56-64 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 18098062-8 2008 It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6. Nicotine 39-47 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 186-192 18041664-3 2007 The absorbed nicotine is rapidly and extensively metabolized to inactive cotinine by CYP2A6 in human livers, which has a major impact on nicotine clearance. Nicotine 13-21 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 85-91 18041664-3 2007 The absorbed nicotine is rapidly and extensively metabolized to inactive cotinine by CYP2A6 in human livers, which has a major impact on nicotine clearance. Nicotine 137-145 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 85-91 18041664-4 2007 Progress has been made in understanding the relationship between the inter-individual variability in nicotine metabolism and genetic polymorphisms of CYP2A6. Nicotine 101-109 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 150-156 17646279-1 2007 Human CYP2A6, which is predominantly expressed in liver, is a key enzyme responsible for the metabolism of nicotine, coumarin, and some pharmaceutical drugs. Nicotine 107-115 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 17267622-1 2007 Human CYP2A6 is responsible for the metabolism of nicotine and its genetic polymorphisms affect smoking behavior and risk of lung cancer. Nicotine 50-58 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 17161559-1 2007 Genetic variation in CYP2A6 (the main nicotine metabolizing enzyme) accounts for some, but not all, of the interindividual and interethnic variability in the rates of nicotine metabolism. Nicotine 38-46 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 17161559-1 2007 Genetic variation in CYP2A6 (the main nicotine metabolizing enzyme) accounts for some, but not all, of the interindividual and interethnic variability in the rates of nicotine metabolism. Nicotine 167-175 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 17979512-3 2007 Cytochrome P450 (CYP)2A6 is the human hepatic enzyme that mediates most of nicotine"s metabolic inactivation to cotinine. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-24 17237153-1 2007 Human CYP2A6 catalyzes the metabolism of nicotine, cotinine, and coumarin as well as some pharmaceutical drugs. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 17267622-4 2007 The plasma cotinine/nicotine ratio in subjects possessing the novel CYP2A6 gene duplication with the CYP2A6*1 allele (10.8 +/- 7.0, n = 4) was 1.4-fold higher than that in homozygotes of the wild type (8.0 +/- 5.0, n = 87), although the difference was not statistically significant. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 68-74 17267622-4 2007 The plasma cotinine/nicotine ratio in subjects possessing the novel CYP2A6 gene duplication with the CYP2A6*1 allele (10.8 +/- 7.0, n = 4) was 1.4-fold higher than that in homozygotes of the wild type (8.0 +/- 5.0, n = 87), although the difference was not statistically significant. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 101-107 17267622-5 2007 The findings in the present study suggested that the novel duplicated CYP2A6 allele, which is specific for African Americans, would increase nicotine metabolism and may affect smoking behavior. Nicotine 141-149 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 70-76 17934923-1 2007 We performed a survey on the relationship between nicotine dependence and psychological (the personality traits using neuroticism extroversion openess-five factor inventory (NEO-FFI)/nicotine metabolism (the CYP2A6 gene polymorphism) factors among Japanese young students to elucidate the mechanism of the development of nicotine dependence. Nicotine 50-58 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 208-214 17178771-1 2007 Human cytochrome CYP2A13 shows overlapping substrate specificity with CYP2A6, catalyzing the metabolism of coumarin, nicotine, cotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Nicotine 117-125 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 70-76 17206525-2 2007 To develop and compare methods that predict individual nicotine (NIC) clearance, which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3"-hydroxycotinine (3HC) measurements. Nicotine 55-63 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 17206525-2 2007 To develop and compare methods that predict individual nicotine (NIC) clearance, which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3"-hydroxycotinine (3HC) measurements. Nicotine 65-68 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 17220563-0 2006 In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais. Nicotine 35-43 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 17130279-0 2007 The role of CYP2A6 in the emergence of nicotine dependence in adolescents. Nicotine 39-47 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 17220563-1 2006 The association between the distribution characteristics of CYP2A6 catalytic activities toward nicotine and coumarin, and the frequency distribution of CYP2A6 variant alleles reported was estimated in 120 healthy Thais. Nicotine 95-103 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 60-66 17220563-4 2006 The inter-individual variability in the in vivo dispositions of coumarin and nicotine closely related to the CYP2A6 genetic polymorphism. Nicotine 77-85 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 109-115 17220563-7 2006 Subjects having CYP2A6*1A/*1B were found to have a higher rate of 7-OHC excretion, as well as a higher cotinine/nicotine ratio in the plasma compared with those of the other genotypes. Nicotine 112-120 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-22 17220563-11 2006 The results of the present study demonstrate that in vivo phenotyping of CYP2A6 using nicotine and coumarin are not metabolically equivalent. Nicotine 86-94 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 73-79 16857725-1 2006 CYP2A6 plays important roles in the metabolism of nicotine and some clinically used drugs. Nicotine 50-58 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 17112802-0 2006 CYP2A6 genotype and the metabolism and disposition kinetics of nicotine. Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 17112802-1 2006 BACKGROUND AND OBJECTIVE: The liver enzyme cytochrome P450 (CYP) 2A6 is primarily responsible for the metabolism of nicotine. Nicotine 116-124 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 43-68 17112802-2 2006 Variants in the CYP2A6 gene have been associated with altered nicotine metabolism and with effects on smoking behavior. Nicotine 62-70 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-22 17112802-3 2006 Our objective was to determine the relationship between variant CYP2A6 genotypes and the disposition and metabolism of nicotine administered intravenously. Nicotine 119-127 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 17112802-6 2006 RESULTS: On the basis of the fractional clearance of nicotine to cotinine and on the plasma ratio of 3"-hydroxycotinine to cotinine, both shown to be indicators of CYP2A6 enzymatic activity, subjects were classified into 3 groups. Nicotine 53-61 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 164-170 17112802-12 2006 CONCLUSIONS: We provide novel pharmacokinetic and metabolic data on nicotine after systemic dosing in relation to common CYP2A6 genotypes. Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 121-127 17125252-1 2006 A series of 3-heteroaromatic analogues of nicotine were synthesized to delineate structural and mechanistic requirements for selectively inhibiting human cytochrome P450 (CYP) 2A6. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 154-179 16636685-1 2006 Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine. Nicotine 44-52 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-31 16636685-2 2006 Genetic polymorphisms of CYP2A6 contribute to the interindividual variability of nicotine metabolism. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 17035386-1 2006 CYP2A6 inactivates nicotine to cotinine and cotinine to 3-hydroxycotinine. Nicotine 19-27 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 17035386-2 2006 We investigated which of plasma nicotine and metabolites were most related to CYP2A6 genotype and smoking levels. Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 78-84 17035386-5 2006 3-Hydroxycotinine/cotinine is reported to be a good marker of CYP2A6 activity, and we found that the 3-hydroxycotinine/(cotinine + nicotine) ratio was most correlated with CYP2A6 genotype (r = 0.38, P < 0.001). Nicotine 131-139 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 172-178 17035386-7 2006 Nicotine metabolism is slower in smokers, and we have shown that CYP2A6 is reduced by nicotine treatment in monkeys. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 17035386-7 2006 Nicotine metabolism is slower in smokers, and we have shown that CYP2A6 is reduced by nicotine treatment in monkeys. Nicotine 86-94 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 17035386-8 2006 Here, we found that plasma nicotine levels were inversely correlated with CYP2A6 activity (3-hydroxycotinine/cotinine, r = -0.41, P < 0.001) among those without CYP2A6 variants, suggesting a reduction in metabolism with higher nicotine levels. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 74-80 17035386-8 2006 Here, we found that plasma nicotine levels were inversely correlated with CYP2A6 activity (3-hydroxycotinine/cotinine, r = -0.41, P < 0.001) among those without CYP2A6 variants, suggesting a reduction in metabolism with higher nicotine levels. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 164-170 17035386-8 2006 Here, we found that plasma nicotine levels were inversely correlated with CYP2A6 activity (3-hydroxycotinine/cotinine, r = -0.41, P < 0.001) among those without CYP2A6 variants, suggesting a reduction in metabolism with higher nicotine levels. Nicotine 230-238 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 74-80 18666753-1 2006 The idea that the liver enzyme cytochrome P450 2A6 (CYP2A6), known also as nicotine C-oxidase, is one of the determinants of smoking addiction and smoking behavior is primarily based on its role in nicotine metabolism and disposition. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-50 16952495-1 2006 Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine and is a possible modulator of nicotine addiction. Nicotine 44-52 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-31 16952495-1 2006 Human cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine and is a possible modulator of nicotine addiction. Nicotine 96-104 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-31 16952495-3 2006 However, there are few data on the ethnic influences of the CYP2A6-nicotine metabolism relationship, particularly with regard to black subjects. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 60-66 16952495-10 2006 These CYP2A6 alleles were associated with reduced nicotine metabolism. Nicotine 50-58 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-12 18666753-1 2006 The idea that the liver enzyme cytochrome P450 2A6 (CYP2A6), known also as nicotine C-oxidase, is one of the determinants of smoking addiction and smoking behavior is primarily based on its role in nicotine metabolism and disposition. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 52-58 18666753-1 2006 The idea that the liver enzyme cytochrome P450 2A6 (CYP2A6), known also as nicotine C-oxidase, is one of the determinants of smoking addiction and smoking behavior is primarily based on its role in nicotine metabolism and disposition. Nicotine 198-206 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-50 18666753-1 2006 The idea that the liver enzyme cytochrome P450 2A6 (CYP2A6), known also as nicotine C-oxidase, is one of the determinants of smoking addiction and smoking behavior is primarily based on its role in nicotine metabolism and disposition. Nicotine 198-206 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 52-58 18666753-6 2006 The results indicate that the phenotype of CYP2A6 enzyme in liver is an outcome of interactions between the CYP2A6 gene, cadmium, nicotine and possibly its metabolites. Nicotine 130-138 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 43-49 18666753-6 2006 The results indicate that the phenotype of CYP2A6 enzyme in liver is an outcome of interactions between the CYP2A6 gene, cadmium, nicotine and possibly its metabolites. Nicotine 130-138 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 108-114 16720336-2 2006 In this study, we have investigated the significance of CYP2A6 genotype on smoking habit and treatment of nicotine patch. Nicotine 106-114 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 56-62 16402128-0 2006 Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Nicotine 64-72 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 17037346-4 2006 Samples were taken from young students of which 87 were smokers and 142 were non-smokers and we tried to clarify the relationship between the nicotine metabolizing ability (CYP2A6), personality, and smoking behavior. Nicotine 142-150 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 173-179 16891249-1 2006 The genetically polymorphic cytochrome P450 (CYP) 2A6 is the major nicotine-oxidase in humans that may contribute to nicotine dependence and cancer susceptibility. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-53 16765148-1 2006 BACKGROUND: Nicotine is metabolized to cotinine, and cotinine is metabolized to 3"-hydroxycotinine (3-HC) by the liver enzyme cytochrome P450 (CYP) 2A6. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 126-151 16402128-0 2006 Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Nicotine 98-106 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 16402128-1 2006 We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in less than or equal to 50% activity, on baseline smoking behaviours and treatment variables in an open-label nicotine replacement therapy (NRT) clinical trial. Nicotine 49-57 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 72-78 16490810-0 2006 Isoflavones inhibit nicotine C-oxidation catalyzed by human CYP2A6. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 60-66 16402086-0 2006 CYP2A6 polymorphisms are associated with nicotine dependence and influence withdrawal symptoms in smoking cessation. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 16402086-1 2006 CYP2A6 is the main enzyme that catalyzes nicotine into cotinine. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 16402086-2 2006 Interindividual differences in nicotine metabolism result at least partially from polymorphic variation of CYP2A6 gene. Nicotine 31-39 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 107-113 16402086-5 2006 Consistent with the previous reports, CYP2A6 genotypes have a tendency to correlate with the number of cigarettes per day and with daily intake of nicotine. Nicotine 147-155 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 16402086-6 2006 Interestingly, CYP2A6 high-activity group (CYP2A6*1/*1, *1/*9, *1/*4, *9/*9) smoked the first cigarette of the day earlier than low-activity group (CYP2A6*4/*9, *4/*4), indicating more remarkable nicotine dependence. Nicotine 196-204 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 15-21 16402086-7 2006 Furthermore, nicotine withdrawal symptoms were more serious in smoking cessation in CYP2A6 high-activity group. Nicotine 13-21 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 16402086-8 2006 Collectively, CYP2A6 genotypes are related with nicotine dependence, influencing smoking habits and withdrawal symptoms in quitting smoking. Nicotine 48-56 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 14-20 16485141-1 2006 RATIONALE: Cyp2a5, the mouse homologue of human CYP2A6, encodes for the enzyme responsible for the primary metabolism of nicotine. Nicotine 121-129 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 48-54 16470306-2 2006 CYP2A6 catalyzes the oxidation of nicotine and the activation of carcinogens such as aflatoxin B1 and nitrosamines. Nicotine 34-42 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 16378601-1 2006 Cytochrome P450 2A6 (CYP2A6) is the major nicotine C-oxidase in human and participates in the metabolism of drugs and precarcinogens. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 16378601-1 2006 Cytochrome P450 2A6 (CYP2A6) is the major nicotine C-oxidase in human and participates in the metabolism of drugs and precarcinogens. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 16188955-0 2006 Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism. Nicotine 42-50 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-22 16599377-2 2006 To investigate the potential mechanism of previously documented lower smoking rates among African-American adolescent smokers seeking cessation treatment, we measured nicotine metabolite ratios as markers of the metabolic disposition of nicotine, which is generally considered to be under the influence of cytochrome P450 (CYP) 2A6. Nicotine 237-245 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 306-331 16188955-2 2006 The primary catalyst of nicotine metabolism in humans is CYP2A6. Nicotine 24-32 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 57-63 16188955-5 2006 Here we report that both CYP2A6 and CYP2A13 were inactivated during nicotine metabolism. Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 16372023-2 2005 METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3"-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke"s Bay Region (6 Maori and 6 European). Nicotine 152-160 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 180-186 16372023-2 2005 METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3"-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke"s Bay Region (6 Maori and 6 European). Nicotine 152-160 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 73-93 16372023-2 2005 METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3"-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke"s Bay Region (6 Maori and 6 European). Nicotine 152-160 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 95-101 16372023-2 2005 METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3"-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke"s Bay Region (6 Maori and 6 European). Nicotine 293-301 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 95-101 16372023-3 2005 RESULTS: (a) The frequencies of the slow nicotine metabolising variants, CYP2A6*9 and *4, were significantly higher in Maori compared to European (p<0.01). Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 73-79 16135656-0 2005 CYP2A6 AND CYP2B6 are involved in nornicotine formation from nicotine in humans: interindividual differences in these contributions. Nicotine 37-45 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 16135656-11 2005 These results as well as the inhibition analyses suggested that CYP2A6 and CYP2B6 would significantly contribute to the nicotine N-demethylation at low and high substrate concentrations, respectively. Nicotine 120-128 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 16135656-9 2005 The nicotine N-demethylase activity in microsomes from 15 human livers at 20 microM nicotine was significantly correlated with the CYP2A6 contents (r = 0.578, p < 0.05), coumarin 7-hydroxylase activity (r = 0.802, p < 0.001), and S-mephenytoin N-demethylase activity (r = 0.694, p < 0.005). Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 131-137 16135656-9 2005 The nicotine N-demethylase activity in microsomes from 15 human livers at 20 microM nicotine was significantly correlated with the CYP2A6 contents (r = 0.578, p < 0.05), coumarin 7-hydroxylase activity (r = 0.802, p < 0.001), and S-mephenytoin N-demethylase activity (r = 0.694, p < 0.005). Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 173-195 16086027-1 2005 Human microsomal cytochrome P450 2A6 (CYP2A6) contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. Nicotine 73-81 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 17-36 16272956-2 2005 Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Nicotine 39-47 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 13-19 16086027-1 2005 Human microsomal cytochrome P450 2A6 (CYP2A6) contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. Nicotine 73-81 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 15671201-1 2005 Nicotine C-oxidation is primarily catalyzed by CYP2A6 in humans. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 47-53 21108885-1 2005 BACKGROUND: Cytochrome P450 2A6 (CYP2A6) plays an important role in oxidation of nicotine and in activation of tobacco-related carcinogens. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-39 16141602-12 2005 Since the genetic polymorphisms of the CYP2A6 gene have a major impact on nicotine clearance, its relationships with smoking behavior or the risk of lung cancer have been suggested. Nicotine 74-82 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 16141602-3 2005 A major pathway of nicotine metabolism is C-oxidation to cotinine, which is catalyzed by CYP2A6 in human livers. Nicotine 19-27 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 89-95 15735609-0 2005 Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 16-22 15848192-0 2005 Modified nicotine metabolism in transgenic tobacco plants expressing the human cytochrome P450 2A6 cDNA. Nicotine 9-17 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 79-98 15735609-5 2005 We review some of the recent findings on the influence of CYP2A6 genetic polymorphisms on nicotine kinetics, smoking behaviors, and how the gene appears to exert differential effects during various stages of smoking (eg, initiation, conversion to dependence, amount smoked during dependence, and quitting). Nicotine 90-98 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 58-64 15735610-2 2005 Cytochrome P450 (CYP) 2A6 is primarily responsible for the metabolism of nicotine. Nicotine 73-81 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-25 15861044-1 2005 Cytochrome P450 2A6 is the main human nicotine metabolizing enzyme coded for by a highly polymorphic gene, CYP2A6. Nicotine 38-46 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 15734728-1 2005 Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 209-215 15734728-8 2005 Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme. Nicotine 48-56 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-37 15861044-1 2005 Cytochrome P450 2A6 is the main human nicotine metabolizing enzyme coded for by a highly polymorphic gene, CYP2A6. Nicotine 38-46 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 107-113 15940289-6 2005 The subjects carrying the CYP2A6*1B allele oxidize nicotine to cotinine faster than subjects with the CYP2A6*1A allele. Nicotine 51-59 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 26-32 15861035-0 2005 Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic influence. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 35-41 15861035-4 2005 DNA was genotyped to confirm zygosity and for variation in the gene for the primary enzyme involved in nicotine metabolism, CYP2A6 (alleles tested: *1, *1x2, *2, *4, *7, *9 and *12). Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 124-130 15658857-0 2005 Quantitative structure-activity relationship analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 97-103 15658857-1 2005 The purpose of this study was to develop screening and in silico modeling methods to obtain accurate information on the active center of CYP2A6, a nicotine oxidizing enzyme. Nicotine 147-155 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 137-143 15658857-6 2005 Potent and specific inhibitors of the CYP2A6 enzyme can be used in the future to increase nicotine bioavailability and thus make oral nicotine administration feasible in smoking cessation therapy. Nicotine 90-98 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 15658857-6 2005 Potent and specific inhibitors of the CYP2A6 enzyme can be used in the future to increase nicotine bioavailability and thus make oral nicotine administration feasible in smoking cessation therapy. Nicotine 134-142 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 38-44 15634016-0 2005 5-substituted, 6-substituted, and unsubstituted 3-heteroaromatic pyridine analogues of nicotine as selective inhibitors of cytochrome P-450 2A6. Nicotine 87-95 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 123-143 15634016-1 2005 A series of 5- and 6-substituted and unsubstituted 3-heteroaromatic analogues of nicotine were synthesized in an effort to delineate the structural requirements for selectively inhibiting human cytochrome P-450 (CYP) 2A6, the major nicotine metabolizing enzyme. Nicotine 81-89 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 194-220 15634016-1 2005 A series of 5- and 6-substituted and unsubstituted 3-heteroaromatic analogues of nicotine were synthesized in an effort to delineate the structural requirements for selectively inhibiting human cytochrome P-450 (CYP) 2A6, the major nicotine metabolizing enzyme. Nicotine 232-240 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 194-220 15634016-5 2005 We identified 36 compounds that were more potent than nicotine at inhibition of coumarin 7-hydroxylase (CYP2A6) activity. Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 80-102 15634016-5 2005 We identified 36 compounds that were more potent than nicotine at inhibition of coumarin 7-hydroxylase (CYP2A6) activity. Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 104-110 15527659-5 2004 DNA was genotyped to confirm zygosity and for variation in the primary gene involved in nicotine metabolism, CYP2A6. Nicotine 88-96 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 109-115 15592323-1 2004 Cytochrome P450 (CYP) 2A6 is a major CYP responsible for the metabolism of nicotine and coumarin in humans. Nicotine 75-83 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-25 15592323-11 2004 For nicotine C -oxidation, the apparent Michaelis-Menten constant values of the wild-type or variant CYP2A6 were 31.6 +/- 2.9 micromol/L and 31.3 +/- 3.1 micromol/L, respectively. Nicotine 4-12 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 101-107 15592323-18 2004 Furthermore, cotinine/nicotine ratios after 1 piece of nicotine gum was chewed, used as an index of in vivo nicotine metabolism, were significantly (P < .05) decreased in heterozygotes of the CYP2A6*17 allele (5.4 +/- 2.7, n = 12) compared with homozygotes of the wild type (11.5 +/- 10.5, n = 37). Nicotine 22-30 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 195-201 15592323-18 2004 Furthermore, cotinine/nicotine ratios after 1 piece of nicotine gum was chewed, used as an index of in vivo nicotine metabolism, were significantly (P < .05) decreased in heterozygotes of the CYP2A6*17 allele (5.4 +/- 2.7, n = 12) compared with homozygotes of the wild type (11.5 +/- 10.5, n = 37). Nicotine 55-63 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 195-201 15592323-18 2004 Furthermore, cotinine/nicotine ratios after 1 piece of nicotine gum was chewed, used as an index of in vivo nicotine metabolism, were significantly (P < .05) decreased in heterozygotes of the CYP2A6*17 allele (5.4 +/- 2.7, n = 12) compared with homozygotes of the wild type (11.5 +/- 10.5, n = 37). Nicotine 55-63 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 195-201 15592323-19 2004 A subject with CYP2A6*17 / CYP2A6*17 revealed the lowest cotinine/nicotine ratio (1.8). Nicotine 66-74 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 15-21 15592323-19 2004 A subject with CYP2A6*17 / CYP2A6*17 revealed the lowest cotinine/nicotine ratio (1.8). Nicotine 66-74 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 15265511-13 2004 This is the first report of the metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted. Nicotine 53-61 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 80-86 15265511-0 2004 Metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted. Nicotine 21-29 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 48-54 15265511-1 2004 Generally, 70-80% of absorbed nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Nicotine 30-38 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 76-101 15265511-4 2004 The purpose of the present study was to clarify the metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted. Nicotine 73-81 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 100-106 15225612-2 2004 CYP2A6 also catalyzes nicotine C-oxidation leading to cotinine formation, a major metabolic pathway of nicotine in humans. Nicotine 22-30 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 15225612-2 2004 CYP2A6 also catalyzes nicotine C-oxidation leading to cotinine formation, a major metabolic pathway of nicotine in humans. Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 15247629-0 2004 Polymorphic NF-Y dependent regulation of human nicotine C-oxidase (CYP2A6). Nicotine 47-55 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 67-73 15247629-1 2004 OBJECTIVES: In humans, cytochrome P450 2A6 (CYP2A6) constitutes the principal nicotine C-oxidase. Nicotine 78-86 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 23-42 15247629-1 2004 OBJECTIVES: In humans, cytochrome P450 2A6 (CYP2A6) constitutes the principal nicotine C-oxidase. Nicotine 78-86 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 44-50 15203795-1 2004 Individuals who carry variant alleles of the CYP2A6 gene are poor metabolizers of nicotine and are believed to be more sensitive to nicotine"s aversive effects than those with normal alleles. Nicotine 82-90 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 45-51 15203795-1 2004 Individuals who carry variant alleles of the CYP2A6 gene are poor metabolizers of nicotine and are believed to be more sensitive to nicotine"s aversive effects than those with normal alleles. Nicotine 132-140 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 45-51 14974084-0 2004 A nicotine C-oxidase gene (CYP2A6) polymorphism important for promoter activity. Nicotine 2-10 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 14974084-1 2004 In humans, several polymorphic variants have been described for the gene encoding the major nicotine C-oxidase, cytochrome P450 2A6 (CYP2A6), which is to a great extent responsible for the large interindividual differences seen at the enzymatic and activity levels. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 112-131 14974084-1 2004 In humans, several polymorphic variants have been described for the gene encoding the major nicotine C-oxidase, cytochrome P450 2A6 (CYP2A6), which is to a great extent responsible for the large interindividual differences seen at the enzymatic and activity levels. Nicotine 92-100 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 133-139 14757175-0 2004 Nicotine-related alkaloids and metabolites as inhibitors of human cytochrome P-450 2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 66-86 14757175-4 2004 beta-Nicotyrine, in which the N-methylpyrrolidino moiety of nicotine was replaced by the aromatic N-methylpyrrole ring, was shown to inhibit human CYP2A6 with much greater potency (Ki=0.37 microM) compared with S-(-)-nicotine. Nicotine 60-68 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 147-153 14757175-4 2004 beta-Nicotyrine, in which the N-methylpyrrolidino moiety of nicotine was replaced by the aromatic N-methylpyrrole ring, was shown to inhibit human CYP2A6 with much greater potency (Ki=0.37 microM) compared with S-(-)-nicotine. Nicotine 211-225 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 147-153 14757175-5 2004 Among the compounds examined, only nicotine and beta-nicotyrine were mechanism-based inhibitors of human CYP2A6. Nicotine 35-43 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 105-111 14757175-7 2004 Our results indicate that the prominent nicotine-related alkaloid beta-nicotyrine present after smoking potently inhibits human CYP2A6. Nicotine 40-48 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 128-134 12406643-5 2002 The resulting interindividual variation in metabolic activity may affect the metabolism of CYP2A6 substrates including nicotine, cotinine (the major metabolite of nicotine), several tobacco-specific procarcinogens, coumarin and many toxins. Nicotine 119-127 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 91-97 14981342-1 2004 The relationship between nicotine metabolism of CYP2A6 and the smoking behavior in a Japanese population was investigated. Nicotine 25-33 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 48-54 12919726-0 2003 Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine, and N-nitrosobenzylmethylamine. Nicotine 93-101 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 58-77 12919726-4 2003 Thus, kinetic parameters were determined for the hydroxylation of five substrates of diverse chemical structures known to be selective for cytochrome P450 2A6: methyl tert-butyl ether (MTBE), nicotine, coumarin, N-nitrosobenzylmethylamine (NBzMA), and N-nitrosodiethylamine (NDEA). Nicotine 192-200 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 139-158 12919726-11 2003 In conclusion, the prototype probes for CYP2A6 phenotyping are coumarin and nicotine. Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 40-46 12844137-1 2003 Cytochrome P450 (CYP) 2A6 catalyzes nicotine C-oxidation, leading to cotinine formation, a major metabolic pathway of nicotine in humans. Nicotine 36-44 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-25 12844137-1 2003 Cytochrome P450 (CYP) 2A6 catalyzes nicotine C-oxidation, leading to cotinine formation, a major metabolic pathway of nicotine in humans. Nicotine 118-126 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-25 12844137-3 2003 Previously, we demonstrated that in vivo nicotine metabolism is impaired with the CYP2A6*4, CYP2A6*7, and CYP2A6*10 alleles in Japanese subjects and Korean subjects. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 82-88 12844137-3 2003 Previously, we demonstrated that in vivo nicotine metabolism is impaired with the CYP2A6*4, CYP2A6*7, and CYP2A6*10 alleles in Japanese subjects and Korean subjects. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 12844137-3 2003 Previously, we demonstrated that in vivo nicotine metabolism is impaired with the CYP2A6*4, CYP2A6*7, and CYP2A6*10 alleles in Japanese subjects and Korean subjects. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 12844137-5 2003 In this study we investigated the effects of the CYP2A6*9 allele on in vivo enzymatic activity by evaluating nicotine metabolism. Nicotine 109-117 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 49-55 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 104-110 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 104-110 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12844137-8 2003 In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 113-119 12832682-1 2003 BACKGROUND: Nicotine is responsible for smoking dependence and is mainly metabolised by CYP2A6. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 88-94 12488541-0 2003 Down-regulation of hepatic nicotine metabolism and a CYP2A6-like enzyme in African green monkeys after long-term nicotine administration. Nicotine 113-121 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 53-59 12488541-2 2003 Nicotine is inactivated to cotinine by CYP2A6 in human liver [nicotine C-oxidation (NCO)]. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 12488541-2 2003 Nicotine is inactivated to cotinine by CYP2A6 in human liver [nicotine C-oxidation (NCO)]. Nicotine 62-70 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 39-45 12488541-4 2003 To evaluate the effects of long-term nicotine treatment on hepatic levels of CYP2A6 and CYP2B6, and nicotine metabolism, an African green monkey (AGM) model was developed. Nicotine 37-45 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 77-83 12488541-14 2003 Consistent with the slower nicotine metabolism observed in smokers, nicotine may decrease its own metabolism in primates by decreasing the expression of the primary nicotine-metabolizing enzyme CYP2A6. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 194-200 12488541-14 2003 Consistent with the slower nicotine metabolism observed in smokers, nicotine may decrease its own metabolism in primates by decreasing the expression of the primary nicotine-metabolizing enzyme CYP2A6. Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 194-200 12488541-14 2003 Consistent with the slower nicotine metabolism observed in smokers, nicotine may decrease its own metabolism in primates by decreasing the expression of the primary nicotine-metabolizing enzyme CYP2A6. Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 194-200 14577978-3 2003 Nicotine is metabolized extensively by the liver enzyme CYP2A6, primarily to cotinine. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 56-62 12749606-1 2003 BACKGROUND: Genetic variation of CYP2A6 is shown to alter nicotine metabolism. Nicotine 58-66 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-39 12708602-5 2003 Additionally, we were interested in the effect of polymorphism on smoking because of the predominant role of CYP2A6 in the metabolism of nicotine. Nicotine 137-145 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 109-115 12504349-2 2003 Hepatic cytochrome P4502A6 (CYP2A6) catalyses the major route of nicotine metabolism: C-oxidation to cotinine, followed by hydroxylation to trans-3"-hydroxycotinine. Nicotine 65-73 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-34 12504349-7 2003 CYP2A6 is highly polymorphic resulting in functional differences in nicotine C-oxidation both in vitro and in vivo; however, population studies fail to consistently and conclusively demonstrate any associations between variant CYP2A6 alleles encoding for either reduced or enhanced enzyme activity with self-reported smoking behaviour. Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 12406643-5 2002 The resulting interindividual variation in metabolic activity may affect the metabolism of CYP2A6 substrates including nicotine, cotinine (the major metabolite of nicotine), several tobacco-specific procarcinogens, coumarin and many toxins. Nicotine 163-171 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 91-97 12406643-6 2002 The frequencies of the CYP2A6 alleles vary considerably among different ethnic populations, which may partially explain the interethnic variability found in CYP2A6-related metabolic activity (e.g. nicotine metabolism), behaviors (i.e. smoking) and disease (i.e. lung cancer). Nicotine 197-205 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 23-29 12406643-6 2002 The frequencies of the CYP2A6 alleles vary considerably among different ethnic populations, which may partially explain the interethnic variability found in CYP2A6-related metabolic activity (e.g. nicotine metabolism), behaviors (i.e. smoking) and disease (i.e. lung cancer). Nicotine 197-205 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 157-163 11684323-1 2001 CYP2A6 (cytochrome P450 2A6), which was first identified as the human coumarin 7-hydroxylase, is the most important enzyme in nicotine C-oxidation. Nicotine 126-134 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 12445030-0 2002 Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Nicotine 60-68 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-37 12445030-2 2002 In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6*4 demonstrated normal nicotine metabolism (CYP2A6*4 is a whole deletion type). Nicotine 115-123 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 74-80 12445030-2 2002 In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6*4 demonstrated normal nicotine metabolism (CYP2A6*4 is a whole deletion type). Nicotine 115-123 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 12445030-2 2002 In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6*4 demonstrated normal nicotine metabolism (CYP2A6*4 is a whole deletion type). Nicotine 115-123 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 12445030-2 2002 In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6*4 demonstrated normal nicotine metabolism (CYP2A6*4 is a whole deletion type). Nicotine 115-123 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 84-90 12445030-2 2002 In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6*4 demonstrated normal nicotine metabolism (CYP2A6*4 is a whole deletion type). Nicotine 202-210 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 74-80 12445030-4 2002 The purpose of the present study was to clarify whether the impaired nicotine metabolism can be ascribed to these CYP2A6 alleles. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 114-120 12445030-5 2002 Furthermore, we also determined whether the subjects possessing CYP2A6*1x2 (duplication) reveal higher nicotine metabolism. Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 12445030-7 2002 RESULTS: The five poor metabolizers were re-genotyped as CYP2A6*7/CYP2A6*4, suggesting that a single nucleotide polymorphism (SNP) causing I471T decreases nicotine metabolism in vivo. Nicotine 155-163 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 57-63 12445030-7 2002 RESULTS: The five poor metabolizers were re-genotyped as CYP2A6*7/CYP2A6*4, suggesting that a single nucleotide polymorphism (SNP) causing I471T decreases nicotine metabolism in vivo. Nicotine 155-163 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 66-72 12445030-8 2002 Furthermore, we found that two subjects out of five with a lower potency of nicotine metabolism possessed SNPs of CYP2A6*7 and CYP2A6*8 simultaneously. Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 114-120 12445030-8 2002 Furthermore, we found that two subjects out of five with a lower potency of nicotine metabolism possessed SNPs of CYP2A6*7 and CYP2A6*8 simultaneously. Nicotine 76-84 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 127-133 12445030-12 2002 The CYP2A6*1x2 allele was found in only one Korean subject (0.5%) whose nicotine metabolic potency was not very high. Nicotine 72-80 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 4-10 12445030-13 2002 CONCLUSIONS: It was clarified that the impaired in vivo nicotine metabolism was caused by CYP2A6*7 and CYP2A6*10 alleles. Nicotine 56-64 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 90-96 12445030-13 2002 CONCLUSIONS: It was clarified that the impaired in vivo nicotine metabolism was caused by CYP2A6*7 and CYP2A6*10 alleles. Nicotine 56-64 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 103-109 12487152-3 2002 Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 46-71 12362322-1 2002 Cytochrome P450 2A6(CYP2A6) is known as a major enzyme responsible for C-oxidation of nicotine and 7-hydroxylation of coumarin. Nicotine 86-94 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-19 12362322-1 2002 Cytochrome P450 2A6(CYP2A6) is known as a major enzyme responsible for C-oxidation of nicotine and 7-hydroxylation of coumarin. Nicotine 86-94 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 20-26 12024803-0 2002 Effects of whole deletion of CYP2A6 on nicotine metabolism in humans. Nicotine 39-47 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 29-35 12024803-1 2002 We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3"-hydroxylating resulted in trans-3"-hydroxycotinine formation. Nicotine 51-59 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 31-37 11805739-0 2002 Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. Nicotine 37-45 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 11805739-3 2002 The genetically polymorphic CYP2A6 enzyme is responsible for the majority of the metabolic inactivation of nicotine to cotinine (12-14). Nicotine 107-115 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-34 11805739-5 2002 CYP2A6 is genetically polymorphic, individuals carrying inactive CYP2A6 alleles have decreased nicotine metabolism, are less likely to become smokers and if they do, they smoke fewer cigarettes per day (13,18,19). Nicotine 95-103 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 11805739-5 2002 CYP2A6 is genetically polymorphic, individuals carrying inactive CYP2A6 alleles have decreased nicotine metabolism, are less likely to become smokers and if they do, they smoke fewer cigarettes per day (13,18,19). Nicotine 95-103 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 65-71 11805739-7 2002 A duplication variant in the CYP2A6 gene locus has been identified which increases nicotine inactivation and increases smoking (19). Nicotine 83-91 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 29-35 11805739-10 2002 Kinetic studies in humans indicated that selective CYP2A6 inhibitors decrease the metabolic removal of nicotine. Nicotine 103-111 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 51-57 11805739-11 2002 It was also shown that inhibiting CYP2A6 in vivo (phenocopying, or mimicking the genetic defect) in smokers results in decreased smoking, making nicotine orally bioavailable, and the rerouting of procarcinogens to detoxifying pathways (20-22). Nicotine 145-153 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 34-40 12487152-5 2002 There are large interindividual differences in nicotine metabolism, and it has been found that the interindividual differences are attributed to the genetic polymorphisms of CYP2A6 gene. Nicotine 47-55 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 174-180 12487152-7 2002 The relationship between CYP2A6 genetic polymorphism and potency of nicotine metabolism, smoking behavior, and cancer risk are extensively reviewed. Nicotine 68-76 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 25-31 12487152-8 2002 Finally, the usefulness of nicotine metabolism for phenotyping of CYP2A6 in individuals and implication of the significance of CYP2A6 genetic polymorphism in a clinical perspective are discussed. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 66-72 12325023-1 2002 The human CYP2A6 enzyme metabolizes certain drugs and pre-carcinogens and appears to be the most important enzyme for nicotine metabolism. Nicotine 118-126 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 10-16 12223434-1 2002 Cytochrome P450 2A6 (CYP2A6) is the principal enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine. Nicotine 178-186 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 11779172-4 2002 Consistent with our homology model predictions, we found (i) that CYP2A6*7 produces an enzyme that has decreased (not inactive) activity for metabolizing nicotine and coumarin; (ii) that CYP2A6*8 is unlikely to affect catalytic activity in vivo; and (iii) that having both substitutions together on an allele (CYP2A6*10) dramatically reduces function and may be fully inactive for some substrates. Nicotine 154-162 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 66-72 11779172-4 2002 Consistent with our homology model predictions, we found (i) that CYP2A6*7 produces an enzyme that has decreased (not inactive) activity for metabolizing nicotine and coumarin; (ii) that CYP2A6*8 is unlikely to affect catalytic activity in vivo; and (iii) that having both substitutions together on an allele (CYP2A6*10) dramatically reduces function and may be fully inactive for some substrates. Nicotine 154-162 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 187-193 11779172-4 2002 Consistent with our homology model predictions, we found (i) that CYP2A6*7 produces an enzyme that has decreased (not inactive) activity for metabolizing nicotine and coumarin; (ii) that CYP2A6*8 is unlikely to affect catalytic activity in vivo; and (iii) that having both substitutions together on an allele (CYP2A6*10) dramatically reduces function and may be fully inactive for some substrates. Nicotine 154-162 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 187-193 11684323-1 2001 CYP2A6 (cytochrome P450 2A6), which was first identified as the human coumarin 7-hydroxylase, is the most important enzyme in nicotine C-oxidation. Nicotine 126-134 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 8-27 11684323-1 2001 CYP2A6 (cytochrome P450 2A6), which was first identified as the human coumarin 7-hydroxylase, is the most important enzyme in nicotine C-oxidation. Nicotine 126-134 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 70-92 11434509-1 2001 CYP2A6 is a major catalyst of nicotine metabolism to cotinine. Nicotine 30-38 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 11353760-1 2001 CYP2A6 is the principle enzyme metabolizing nicotine to its inactive metabolite cotinine. Nicotine 44-52 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 11353760-9 2001 R-(+)-Tranylcypromine, (+/-)-tranylcypromine, and S-(-)-tranylcypromine competitively inhibited CYP2A6-mediated metabolism of nicotine with apparent K(i) values of 0.05, 0.08, and 2.0 microM, respectively. Nicotine 126-134 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 96-102 11353760-10 2001 Tranylcypromine [particularly R-(+) isomer], tryptamine, and methoxsalen are specific and relatively selective for CYP2A6 and may be useful in vivo to decrease smoking by inhibiting nicotine metabolism with a low risk of metabolic drug interactions. Nicotine 182-190 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 115-121 11394901-1 2001 Human cytochrome P450 2A6 (CYP2A6) constitutes the major nicotine oxidase, and large interindividual differences are seen in the levels of this enzyme, to a great extent caused by the distribution of several different polymorphic gene variants mainly located in the open reading frame (ORF). Nicotine 57-65 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 6-25 11394901-1 2001 Human cytochrome P450 2A6 (CYP2A6) constitutes the major nicotine oxidase, and large interindividual differences are seen in the levels of this enzyme, to a great extent caused by the distribution of several different polymorphic gene variants mainly located in the open reading frame (ORF). Nicotine 57-65 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 27-33 11434509-2 2001 Previously, we demonstrated that the interindividual difference in nicotine metabolism is related to a genetic polymorphism of the CYP2A6 gene in Japanese. Nicotine 67-75 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 131-137 11434509-11 2001 It was confirmed that the interindividual difference in nicotine metabolism was closely related to the genetic polymorphism of CYP2A6. Nicotine 56-64 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 127-133 11197315-1 2000 Extant data, mostly from studies in vitro, suggest that coumarin and nicotine are both metabolized by CYP2A6, a cytochrome P450 isozyme. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 102-108 11241319-1 2001 Cytochrome P450 2A6 (CYP2A6) plays an important role in the oxidation of nicotine and in the activation of tobacco-related carcinogens, such as N-nitrosodimethylamine, N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Nicotine 73-81 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 11207029-1 2001 Cytochrome P450 2A6 (CYP2A6) is involved in the C-oxidation of nicotine and in the metabolic activation of tobacco nitrosamines. Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 21-27 11180041-0 2001 Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans. Nicotine 52-60 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 76-82 11180041-1 2001 BACKGROUND: Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Nicotine 12-20 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 58-83 11180041-2 2001 Previously, we found that the CYP2A6 gene was deleted homozygously in one subject who was deficient in cotinine formation from nicotine. Nicotine 127-135 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 30-36 11180041-3 2001 OBJECTIVE: Our objective was to clarify the relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism. Nicotine 96-104 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 120-126 11180041-13 2001 The probit plot of the cotinine-nicotine ratio was not linear; this possibly indicated the existence of a novel mutation in the CYP2A6 gene genotyped as CYP2A6*1B/CYP2A6*4. Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 128-134 11180041-13 2001 The probit plot of the cotinine-nicotine ratio was not linear; this possibly indicated the existence of a novel mutation in the CYP2A6 gene genotyped as CYP2A6*1B/CYP2A6*4. Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 153-159 11180041-13 2001 The probit plot of the cotinine-nicotine ratio was not linear; this possibly indicated the existence of a novel mutation in the CYP2A6 gene genotyped as CYP2A6*1B/CYP2A6*4. Nicotine 32-40 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 153-159 11180041-14 2001 CONCLUSIONS: The relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans was proved. Nicotine 69-77 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 93-99 11259349-0 2001 Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk. Nicotine 25-33 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 9-15 11259349-2 2001 In humans, 70 to 80% of nicotine is metabolized to the inactive metabolite cotinine by the enzyme CYP2A6. Nicotine 24-32 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 98-104 11259349-4 2001 In initial studies we found that there was an under-representation of individuals carrying defective CYP2A6 alleles in a tobacco-dependent population, and that among smokers, those with deficient nicotine metabolism smoked fewer cigarettes. Nicotine 196-204 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 101-107 11259349-8 2001 Both kinetic and behavioral experiments in human smokers demonstrated that inhibiting CYP2A6 in vivo decreased nicotine metabolism and smoking behavior. Nicotine 111-119 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 86-92 11237731-1 2001 CYP2A6 is known as a major cytochrome P450 (CYP) responsible for the oxidation of nicotine and coumarin in humans. Nicotine 82-90 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 11237731-7 2001 These data suggest that individuals homozygous for the T1412C variant allele or heterozygous for this and a defect allele such as the CYP2A6*4 may be poor metabolizer of nicotine, but not coumarin. Nicotine 170-178 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 134-140 11159795-0 2001 Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. Nicotine 112-120 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 29-48 11159795-0 2001 Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. Nicotine 112-120 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 50-56 11159795-1 2001 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. Nicotine 175-183 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-52 11159795-1 2001 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. Nicotine 175-183 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 54-60 11159795-1 2001 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. Nicotine 175-183 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 62-84 11159795-6 2001 Because of the importance of CYP2A6 in nicotine metabolism, it has been suggested that the CYP2A6 genotype influences the interindividual differences in smoking behavior as well as lung cancer susceptibility. Nicotine 39-47 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 29-35 11159795-6 2001 Because of the importance of CYP2A6 in nicotine metabolism, it has been suggested that the CYP2A6 genotype influences the interindividual differences in smoking behavior as well as lung cancer susceptibility. Nicotine 39-47 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 91-97 11050152-0 2000 2"-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: formation of a lung carcinogen precursor. Nicotine 20-28 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 32-51 11050152-5 2000 Incubation of nicotine with cytochrome P450 2A6 and cofactors did indeed produce aminoketone, which was identified as its N-benzoyl derivative by GC-MS. Nicotine 14-22 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-47 11197315-6 2000 The results support previous in vitro findings that both coumarin and nicotine are metabolized, at least in part, by a common pathway, which most likely is CYP2A6. Nicotine 70-78 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 156-162 11281276-5 2000 This suggests that a smoking subject with a genotype predicted to confer 50% of the ability to eliminate nicotine via the CYP2A6 pathway has almost twice the likelihood of quitting smoking. Nicotine 105-113 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 122-128 10999944-1 2000 In humans, 80% of nicotine is metabolized to the inactive metabolite cotinine by the enzyme CYP2A6, which can also activate tobacco smoke procarcinogens (e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). Nicotine 18-26 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 10999944-2 2000 Previously, we demonstrated that individuals who are nicotine-dependent and have defective CYP2A6 alleles (*2, *3) smoked fewer cigarettes; however, we recognize that the genotyping method used for the CYP2A6*3 allele gave a high false-positive rate. Nicotine 53-61 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 91-97 10999944-2 2000 Previously, we demonstrated that individuals who are nicotine-dependent and have defective CYP2A6 alleles (*2, *3) smoked fewer cigarettes; however, we recognize that the genotyping method used for the CYP2A6*3 allele gave a high false-positive rate. Nicotine 53-61 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 202-208 10510277-1 1999 Cytochrome P450 (CYP) 2A6 is the principal human enzyme catalyzing coumarin 7-hydroxylation and is known to be involved in the metabolism of halothane, nicotine, and metabolic activation of butadiene and nitrosamines. Nicotine 152-160 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-25 10781881-3 2000 CYP2A6 is a major contributor to the oxidative metabolism of nicotine and cotinine, and it also contributes, to a larger or smaller extent, to the metabolism of a few pharmaceuticals (e.g. fadrozole), nitrosamines, other carcinogens (e.g. aflatoxin B1) and a number of coumarin-type alkaloids. Nicotine 61-69 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 10565842-9 1999 We conclude that the metabolism of cotinine is slower in blacks than in whites because of both slower oxidative metabolism of nicotine to cotinine (presumably via cytochrome P-450 2A6) and slower N-glucuronidation. Nicotine 126-134 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 163-183 10544257-0 1999 Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. Nicotine 96-104 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 66-71 10544257-4 1999 Among Caucasians, an additional defective and frequently distributed allele (CYP2A6*3) has been suggested to play a protective role against nicotine addiction and cigarette consumption. Nicotine 140-148 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 77-83 10663384-9 2000 Kinetic analysis showed that two CYP2A6(*)1/(*)2 individuals had a very low ratio of V(max) to K(m) for nicotine C-oxidation as well as coumarin 7-hydroxylation in liver microsomes, compared with those of homozygous CYP2A6(*)1-type. Nicotine 104-112 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 33-39 10663384-9 2000 Kinetic analysis showed that two CYP2A6(*)1/(*)2 individuals had a very low ratio of V(max) to K(m) for nicotine C-oxidation as well as coumarin 7-hydroxylation in liver microsomes, compared with those of homozygous CYP2A6(*)1-type. Nicotine 104-112 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 216-222 10668854-0 2000 Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans. Nicotine 34-42 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 86-92 10668854-1 2000 Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 46-71 10448083-0 1999 The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP. Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 35-41 10448083-0 1999 The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP. Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 102-108 10448083-7 1999 This study provides a firm experimental basis for correlating genotypic characterization of CYP2A6 with phenotypic expression of nicotine metabolism. Nicotine 129-137 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 10350185-0 1999 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Nicotine 30-38 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 9-15 10350185-8 1999 These results support the view that CYP2A6 has major roles for nicotine C-oxidation at lower substrate concentration and both CYP2A6 and 2B6 play roles at higher substrate concentrations in human liver microsomes. Nicotine 63-71 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 36-42 10350185-5 1999 In liver microsomes of 16 human samples, nicotine C-oxidation activities were correlated with CYP2A6 contents at 10 microM substrate concentration, whereas such correlation coefficients were decreased when the substrate concentration was increased to 500 microM. Nicotine 41-49 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 94-100 10350185-6 1999 Contribution of CYP2B6 (as well as CYP2A6) was demonstrated by experiments with the effects of orphenadrine (and also coumarin and anti-CYP2A6) on the nicotine C-oxidation activities by human liver microsomes at 500 microM nicotine. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 35-41 10350185-6 1999 Contribution of CYP2B6 (as well as CYP2A6) was demonstrated by experiments with the effects of orphenadrine (and also coumarin and anti-CYP2A6) on the nicotine C-oxidation activities by human liver microsomes at 500 microM nicotine. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 136-142 10350185-6 1999 Contribution of CYP2B6 (as well as CYP2A6) was demonstrated by experiments with the effects of orphenadrine (and also coumarin and anti-CYP2A6) on the nicotine C-oxidation activities by human liver microsomes at 500 microM nicotine. Nicotine 223-231 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 35-41 9827545-2 1998 The role of CYP2A6 for nicotine elimination was emphasised recently by the finding that smokers carrying defective CYP2A6 alleles consumed fewer cigarettes [Pianezza et al. Nicotine 23-31 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 12-18 11768189-2 1999 CYP2A6 is the enzyme responsible for the majority of the inactivation of nicotine in humans. Nicotine 73-81 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 11768189-8 1999 We also discuss recent findings which suggest that mimicking this gene defect by inhibiting CYP2A6 decreases nicotine metabolism and smoking. Nicotine 109-117 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 92-98 11768189-9 1999 Further research is needed in order to improve our understanding of how genetic variation in CYP2A6 alters the risk for nicotine dependence and lowers nicotine consumption. Nicotine 120-128 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 93-99 11768189-9 1999 Further research is needed in order to improve our understanding of how genetic variation in CYP2A6 alters the risk for nicotine dependence and lowers nicotine consumption. Nicotine 151-159 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 93-99 9143352-7 1997 The following chemicals were classified as strong inhibitors of CYP2A6 (defined by Ki < 200 microM): clotrimazole, diethyldithiocarbamate, ellipticine, ketoconazole, 8-methoxypsoralen, 4-methylpyrazole, metyrapone, miconazole, alpha-naphthoflavone, nicotine, p-nitrophenol, and tranylcypromine. Nicotine 252-260 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 64-70 9316878-0 1997 A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes. Nicotine 27-35 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 17-23 9316878-7 1997 CYP2A6 appears to be the major P450 involved in human nicotine metabolism to cotinine. Nicotine 54-62 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 0-6 9316878-11 1997 Immunochemically determined CYP2A6 correlated significantly with nicotine-to-cotinine V(max) values (r = .90, n = 30, P < .001) and to inhibition of nicotine metabolism by coumarin (r = .94, n = 30, P < .001). Nicotine 65-73 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-34 9316878-11 1997 Immunochemically determined CYP2A6 correlated significantly with nicotine-to-cotinine V(max) values (r = .90, n = 30, P < .001) and to inhibition of nicotine metabolism by coumarin (r = .94, n = 30, P < .001). Nicotine 152-160 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 28-34 9316878-12 1997 These data indicate that nicotine metabolism is highly variable among individual livers and that this is due to variable expression of CYP2A6, not CYP2D6. Nicotine 25-33 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 135-141 8937855-6 1996 When the capability of microsomes of B-lymphoblastoid cells expressing human CYPs to perform biotransformation of nicotine to cotinine was determined, cDNA-expressed CYP2A6 exhibited the highest cotinine formation. Nicotine 114-122 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 166-172 8937855-9 1996 Nicotine is a new in vivo probe for phenotyping of CYP2A6 in humans. Nicotine 0-8 cytochrome P450 family 2 subfamily A member 6 Homo sapiens 51-57