Polymorphic N-acetylation of a caffeine metabolite

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Abstract
In the course of investigations into variability in the metabolism of caffeine [a central stimulant] in human populations, urinary levels of 5-acetylamino-6-formylamino-3-methyluracil (AFMU), a newly discovered ring-opened metabolite of caffeine, were both bimodally distributed and interethnically variable in samples (Caucasian: n = 42; Oriental: n = 26) from the Toronto population. To test the premise that the polymorphic N-acetyltransferase enzyme (EC 2.3.1.-) could be responsible for the production of AFMU, 20 of the subjects were phenotyped for acetylator status using sulfamethazine (SMZ). Concordance for all subjects between AFMU production and SMZ acetylation strongly suggests that the acetylation polymorphism is involved in the formation of AFMU in man.