Regular ArticleOxidation of Caffeine to Theobromine and Theophylline Is Catalyzed Primarily by Flavin-Containing Monooxygenase in Liver Microsomes☆
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Xanthine scaffold: scope and potential in drug development
2018, HeliyonCitation Excerpt :Among natural xanthine derivatives caffeine is a major component for biotransformation into its different metabolites. In mammalian system, natural xanthine derivative caffeine is biotransformed in liver cells by the catalytic action of cytochrome P450 enzyme into three primary metabolites: paraxanthine (84%), theobromine (12%), and theophylline (4%) as shown in Fig. 3 [67,68]. The caffeine biotransformation in plant parts like coffee fruits and leaves proceeds via theobromine, theophylline, 3-methylxanthine, 7-methylxanthine, xanthine, allantoin, allantoic acid and urea [58, 69, 70, 71].
Quantum chemical exploration on the metabolic mechanisms of caffeine by flavin-containing monooxygenase
2016, TetrahedronCitation Excerpt :The four important primary metabolites of caffeine are theophylline (TP, 1,3-dimethylxanthine), paraxanthine (PX, 1,7-dimethylxanthine) and theobromine (TB, 3,7-dimethylxanthine), formed by N-demethylation at each of the three tertiary amine nitrogen atoms, as well as 1,3,7-trimethyluric acid (TMU) formed by C-8 oxidation.16,17 Bioconversion of caffeine into its metabolites is an enzymatic process and occurs primarily in the liver.18 Two main types of enzymes presented in the liver microsomes of human can potentially catalyze the metabolism of caffeine, namely, flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP).19,20
Antioxidant activity elicited by low dose of caffeine attenuates pentylenetetrazol-induced seizures and oxidative damage in rats
2013, Neurochemistry InternationalCitation Excerpt :This idea is largely based on chemical studies showing it to be able to scavenge ROS, particularly the hydroxyl radical (OH) in vitro (Devasagayam et al., 1996; Gomez-Ruiz et al., 2007). The interaction of OH with caffeine results in its oxidative de-methylation generating partially N-methylated xanthines such as theobromine, paraxanthine, and theophylline (Chung and Cha, 1997; Stadler et al., 1996). In addition, studies have shown that the antioxidant effect of caffeine is similar to that of glutathione and higher than that of ascorbic acid (Devasagayam et al., 1996).
Alteration of xenobiotic metabolizing enzymes by resveratrol in liver and lung of CD1 mice
2009, Food and Chemical ToxicologyRelative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: The pathway and concentration dependence
2008, Biochemical PharmacologyCitation Excerpt :As shown in our present work, CYP1A2 is the major enzyme catalyzing caffeine 8-hydroxylation at a concentration of 100 μM (relevant to “the maximum therapeutic concentration in humans”), but the contribution of CYP3A2 to 8-hydroxylation markedly rises at higher substrate concentrations at the expense of CYP1A2. Our results do not closely correspond, either, to the findings of Chung et al. [11,19] who proposed – on the basis of unspecific P450 and FMO inducers/inhibitors [45] and using the very high 10 mM concentration of caffeine – that caffeine 8-hydroxylation was catalyzed mainly by CYP2B1, CYP3A1, CYP2E1, while N-demethylation reactions by CYP1A2 and FMO. Our present study indicates that FMO does not significantly contribute to caffeine metabolism measured in vitro at the substrate concentration of 100 μM, as shown by the thermal inactivation of FMO.
Perturbation of murine liver cyp-superfamily of isoforms by different combinations of pesticide mixtures
2008, Food and Chemical Toxicology
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W. B. Jakoby, Ed.
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