Oxidative caffeine degradation

Experiments with liver slices and cultured cell lines have corroborated this pathway of purine degradation. In human liver slices 16 xanthine derivatives were produced from caffeine by action of P-450 system. Demethylation at N-3 was the most prominent process [18, 19]. Comparison of cell lines from humans, hamsters, mice, and rats show some interspecies differences but all of them demethylated and oxidized caffeine [20]. Human liver cells give 1,3,7-trimethylurate as the major metabolite of caffeine, but also made were the intermediate products theobromine, theophylline, and paraxanthine [21]. Human liver microsomes convert theophylline to 1-methylxanthine, 3-methylxanthine, and 1,3-dimethyluric acid [22, 23]. Human kidney microsomes produced each of the three possible demethylated products as well as 1,3,7-... 

Fig. 293 3-Methylxanthme, 1-methylxanthine, and theophylline are synthesized fiom caffeine as part of the caffeine degradation pathway that produces xanthine which is further degraded to CO2 and NH3 by the craivcaitional oxidative piuine catabolism pathway. The conversion of caffeine to theophylline is the rate-limiting step in caffeine-accumulating species such as Coffea arabica and Camellia sinensis. Solid arrows indicate major routes and dotted arrow minor conversions. The pathway was elucidated from data obtained in feeding experiments. Y-Demethylase enzymes involved in caffeine degradation have not yet been characterized in plants. Enzymes NDM iV-demethylase, XDH xanthine dehydrogenase...

Alcohols are oxidized to aldehydes by the liver enzyme alcohol dehydrogenase, and aldehydes to carboxylic acids by aldehyde dehydrogenase. In mammals, monooxygenases can be induced by plant secondary metabolites such as a-pinene, caffeine, or isobornyl acetate. Reduction is less common and plays a role with ketones that cannot be further oxidized. Hydrolysis, the degradation of a compound with addition of water, is also less common than oxidation. 

Methylated xanthines like caffeine are degraded in humans and rats by oxidative removal of methyl groups [10], Thus caffeine goes to 1,7-dimethylxanthine and 1-methylxanthine [11]. After the first demethylation there is an alternate pathway producing 5-acetylamino-6-formylamino-3-methyluracil. This pathway is more active in people with a more active acetylation system [12, 13]. There are individual, quantitative differences in the activity of this pathway in humans. In rats a major metabolite is... 

Xanthine, or 2,6-dihydroxypurine, was first associated with caffeine in certain plants. It was later found in urine, blood, and liver. In 1817, Marcet detected xanthine in renal calculi. Xanthine was synthesized from chloropurine or from 4-aminouracil. An addition to its biological significance as the product of nucleic acid degradation (deamination of guanine or oxidation of hypoxanthine), xanthine is also important as an... 

N -methylxanthine (II) which is subsequently demethylated at the N -position (III) and remethylated on C-2 to form the methoxy derivative (IV) and oxidized on C-8 (V) which can be converted to compound VI, which is one of the compounds recently isolated (see Fig. 6.27c, Wanner et aL, 1975) (2) the direct conversion to compound VI which can proceed by several alternate pathways. Compound VI can be oxidized to allantoin (VII) and allantoic acid (VIII) and then to CO2 (IX). Caffeine may be degraded by an unknown pathway into allantoin, allantoic acid, and finally, to CO2. 

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