Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. Purpose . The enzyme efficiency varies between individuals. The CYP1A2*1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles or haplotype might increase or decrease caffeine metabolism. Furthermore, rates of caffeine metabolism vary between individuals, as caffeine half-life values ranging from 1.5 to 9.5 hours have been reported. The single nucleotide polymorphism (SNP) rs762551A>C, which has also been studied for its modifying effect on cardiovascular disease, has been reported to alter enzyme activity. CYP1A2 encodes for an enzyme (cytochrome P450 family 1 subfamily A member 2) and catalyzes reactions involved in drug metabolism and synthesis of cholesterol, steroids, substances, and other lipids (). Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Theophylline and melatonin are also sometimes used as probe drugs whereas in vitro studies often use phenacetin [Article:18466106]. Function. Results: ... CYP1A2 enzymatic metabolism of caffeine in the liver to produce the three major caffeine metabolites, paraxanthine, theophylline and theobromine. Caffeine metabolism: Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. Coffee is the primary source of caffeine for Americans. 21-23 An A→C substitution at position 734 (CYP1A2*1F) in the CYP1A2 gene decreases enzyme inducibility as measured by the … The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Because CYP1A2 rs762551 variant and caffeine-GS were highly correlated (P < 1.0 × 10 –300), and the functional effect on caffeine metabolism has been determined only for CYP1A2 in a caffeine challenge test (10, 11), our primary analyses were based on CYP1A2, and caffeine-GS was considered as a secondary genetic determinant of caffeine metabolism. One drawback of such testing is that the subject must abstain from coffee, many teas and soft drinks, and chocolate for a day or so before the test. Paraxanthine (1,7-dimethylxanthine), a metabolite from 3-N-demethylation of caffeine, was measured to … Caffeine is metabolized primarily by cytochrome P450 1A2 (CYP1A2) in the liver through an initial N 3-demethylation. Several genes are involved in eliciting the different responses to caffeine among individuals. The interaction of caffeine with fluvoxamine, a strong CYP1A2 inhibitor, suggested a 93% contribution of CYP1A2 to caffeine metabolism in healthy subjects (Culm-Merdek et al., 2005). Coffee and Caffeine Genetics Consortium et al. The objective of this study was to determine whether variation in the CYP1A2 gene, which affects caffeine metabolism, modifies the ergogenic effects of caffeine in a 10-km cycling time trial. The cytochrome P450 enzyme CYP1A2 plays a major role in metabolism of many commonly used drugs including clozapine, imipramine, caffeine, paracetamol, phenacetin, theophylline, tacrine [ 1], and some neurotoxins [ 2].Furthermore, CYP1A2 activates several aromatic amines and thus is a key enzyme in chemical carcinogenesis [ 3]. Although this polymorphism has been known to influence the inducibility of hepatic CYP1A2 and the rate of caffeine metabolism, levels of caffeine and/or metabolites have never been reported in these aforementioned studies (1, 12, 16). Hypersensitivity to caffeine: These people have very low CYP1A2 activity. Caffeine is a chemical compound which acts as a stimulant when consumed. Material and Methods: Twenty male subjects participated in two 3 km cycling time trials 60 minutes following placebo (all-purpose flour) and caffeine (6 mg/kg BW anhydrous caffeine) supplementation. Home; How it works; Genes we analyze; CYP1A2; Caffeine has been used by athletes for a long time as a performance-enhancing drug. CYP1A2 is responsible for more than 95% of the primary metabolism of caffeine [Article:8491061]. These issues include the potential influence of a methylxanthine abstinence period prior to caffeine CYP1A2 phenotyping and the impact of caffeine formulation on determining CYP1A2 activity. The gene CYP1A2 encodes cytochrome P450 1A2, an enzyme responsible for up to 95% of caffeine metabolism . Caffeine is a stimulant and the most commonly used drug on the planet. Caffeine metabolism at rest over a similar seven hour period was also determined in the same manner. This first variant is very well studied for the speed of caffeine metabolism. The CYP1A2 gene controls the activity of the cytochrome P450 1A2 enzyme, which is responsible for nearly all of our metabolic processing of caffeine. Increased risk of recurrent pregnancy loss induced by caffeine ( Sata et al., 2005 ) and more recently decreased risk of nonfatal MI induced by caffeine ( Cornelis et al., 2006 ) have been associated with CYP1A2*1F allele. Two variants of the gene exist: the CPA1A2*1A allele results in fast caffeine metabolism, while the CPA1A2*1F allele results in slower caffeine metabolism. Unfortunately, about 50 percent of the population has a variant in the CYP1A2 gene that leads to slow processing of caffeine. What is the association between CYP1A2 and caffeine metabolism?. For example, narigenin, the chemical that makes grapefruit juice bitter, by inhibiting the production of CYP1A2, slows the clearance of caffeine from the body and prolongs its half-life by over 30%! Studies have shown that taking caffeine before exercise improves performance. Molecular Genetics Shahidi (1967) described the familial occurrence of acetophenetidin susceptibility, suggesting genetic factors in the effects of CYP1A2. Normal sensitivity to caffeine: This is the vast majority of people.They can consume up to 400 mg of caffeine per day without adverse side effects. For these “slow metabolizers,” drinking coffee: Background: The enzyme CYP1A2 (cytochrome 1A2) is involved in the metabolism of certain drugs and caffeine, and its activity can be influenced by factors such as sex, age, and smoking. In the body, CYP1A2 accounts for around 95% of caffeine metabolism.. 20,21 CYP1A2 accounts for approximately 95% of caffeine metabolism and demonstrates wide variability in enzyme activity between individuals. Metabolism of caffeine by the CYP1A2 enzyme shows substantial variation between people, 41, 42 because of both genetic and environmental factors. It represents 15% of all cytochrome P450 in the human liver and accounts for more than 90% of caffeine metabolism (Arnaud, 2011). Abstract Purpose Many studies have examined the effect of caffeine on exercise performance, but findings have not always been consistent. Cornelis MC et al. Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism. CYP1A2 is an enzyme found primarily in the liver that affects the metabolism of substrates such as estradiol (estrogen), propranolol (heart medication), caffeine and Cymbalta (antidepressant). A homozygous, that is, AA genotype represents individuals that can rapidly metabolize caffeine. CYP1A2 catalyzes the 1-, 3-, and 7-demethylations of caffeine, the 7-demethylation of paraxanthine, and the 1- … "Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption." Prior studies from our laboratory suggest that the -163 C > A polymorphism of the Cytochrome P450 (CYP1A2) gene influences the ergogenic effect of caffeine. Estimated CYP1A2 enzyme activity, and thus speed of caffeine metabolism, was higher in our type-2 diabetes group; this was possibly due to higher intake of caffeine, a known inducer of CYP1A2 enzyme activity. CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. Context: The association between coffee intake and risk of myocardial infarction (MI) remains controversial. The influence of CYP1A2 genotype in the basal and post-caffeine blood pressure response to caffeine ingestion is modified by physical activity status and caffeine consumption level. The speed of caffeine metabolism is affected by a single nucleotide polymorphism, rs762551, within this gene . The objective of this study was to determine whether variation in the CYP1A2 gene, which affects caffeine metabolism, modifies the ergogenic effects of caffeine in a 10-km cycling time trial.. Methods . Introduction. (2015). CYP1A2 A gene for caffeine metabolism. Caffeine metabolism and t he CYP enzymes responsi ble for transf ormation to i ts primary m etabolit es have bee n studie d in vitro , using human l iver micros omes and expres sion of CYP1A2 cDNA It has also prompted a closer look at the effects of caffeine on exercise. Sachse C, Bhambra U, Smith G et al. Individuals who have two copies of the fast CYP1A2*1A allele are fast caffeine metabolizers; whereas people who have at least one copy of the slow CYP1A2*1F allele are slow caffeine metabolizers. This is because CYP1A2 turns the pro-carcinogenic molecules into carcinogens, which then have to be removed from the body. They have a strong response to even small amounts of caffeine, and will commonly experience jitters and insomnia. The enzyme CYP1A2 is involved in the metabolism of certain drugs and caffeine. CYP1A2 drug metabolism. CYP1A2 Genetic Variants: One of the fun things to find out from your CYP1A2 genes is whether you are a fast or slow metabolizer of caffeine. Given the fairly small sample sizes, the results need to be considered as preliminary and require validation in larger populations. (2016). Furthermore, questions regarding the appropriate study design and methodology to conduct studies to evaluate CYP1A2 activity have often been overlooked. Scientists are now studying whether the CYP1A2 gene and others might mediate coffee’s influence on breast and ovarian cancer, Type 2 diabetes and even Parkinson’s disease. Genetics of Caffeine Consumption. Caffeine is the main probe drug used to assess CYP1A2 activity in vivo. 20(5):647-56. Some individuals have a mutation in this locus and thus have the AC genotype. CYP1A2 is found only in the liver. The purpose of this study was to determine whether CYP1A2 polymorphism affects caffeine metabolism and subsequent exercise performance between the genotypes (AA homozygotes and C allele carriers). For a 53% enzyme contribution, the AUC increase will be less than 2-fold and will have a weak effect. Mol Psychiatry. One proposed phenotyping method for CYP1A2 is to obtain a saliva sample following a test dose of caffeine. The metabolites are predominantly catalyzed by CYP3A4 (77% approximately 87%), with a moderate contribution from CYP3A5 (5% approximately 15%) and CYP1A2 (3.7% approximately 7.5%). Caffeine is metabolized by an enzyme in the liver that is encoded for by the CYP1A2 gene. One is the CYP1A2 gene that encodes for a liver enzyme critical for the metabolism of caffeine. Caffeine (1,3,7-trimethylxanthine) was used as the substrate of CYP1A2. 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