Paraxanthine is not produced by plants and is only observed in nature as a metabolite of caffeine in animals. Paraxanthine is also a natural metabolite of caffeine in some species of bacteria. After intake, roughly 84% of caffeine is demethylated at the 3-position to yield paraxanthine, making it the chief metabolite of caffeine in the body.
Paraxanthine is also a major metabolite of caffeine in humans and other animals, such as mice. Shortly after ingestion, caffeine is metabolized into paraxanthine by hepatic cytochrome P450, which removes a methyl group from the N3 position of caffeine. After formation, paraxanthine can be broken down to 7-methylxanthine by demethylation of the N1 position, which is subsequently demethylated into xanthine or oxidized by CYP2A6 and CYP1A2 into 1,7-dimethylaric acid. In another pathway, paraxanthine is broken down into 5-acetylamino-6-formylamino-3-methyluracil through N-acetyl-transferase 2, which is then broken down into 5-acetylamino-6-amino-3-methyluracil by non-enzymatic decomposition. In yet another pathway, paraxanthine is metabolized CYPIA2 forming 1-methyl-xanthine, which can then be metabolized by xanthine oxidase to form 1-methyl-uric acid.
Certain proposed synthetic pathways of caffeine make use of paraxanthine as a bypass intermediate. However, its absence in plant alkaloid assays implies that these are infrequently, if ever, directly produced by plants.
Pharmacology and Physiological Effects
Paraxanthine may be responsible for the lipolytic properties of caffeine, and its presence in the blood causes an increase in serum free fatty acid concentration.
Paraxanthine is believed to exhibit a lower toxicity than caffeine. While blood levels commensurate with average intake appear to be fairly innocuous, high blood concentrations of paraxanthine have been linked to miscarriage in pregnant mothers.
^ abMazzafera P (May 2004). "Catabolism of caffeine in plants and microorganisms". Frontiers in Bioscience. 9: 1348–59. doi:10.2741/1339. PMID14977550.
^Fuhr U, Doehmer J, Battula N, Wölfel C, Flick I, Kudla C, Keita Y, Staib AH (October 1993). "Biotransformation of methylxanthines in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Allocation of metabolic pathways to isoforms and inhibitory effects of quinolones". Toxicology. 82 (1–3): 169–89. doi:10.1016/0300-483x(93)90064-y. PMID8236273.
^Graham TE, Rush JW, van Soeren MH (June 1994). "Caffeine and exercise: metabolism and performance". Canadian Journal of Applied Physiology. 19 (2): 111–38. doi:10.1139/h94-010. PMID8081318.
^ abCaffeine : chemistry, analysis, function and effects. Preedy, Victor R.,, Royal Society of Chemistry (Great Britain),. Cambridge, U.K. ISBN9781849734752. OCLC810337257.CS1 maint: extra punctuation (link) CS1 maint: others (link)