Acetylator phenotyping: the urinary caffeine metabolite ratio in slow acetylators correlates with a marker of systemic NAT1 activity.
Eighteen healthy Caucasians were evaluated for the systemic acetylation of a caffeine metabolite using the urinary caffeine metabolite ratio 5-acetylamino-6-formylamino-3-methyluracil (AFMU) to 1-methylaxanthine (1X) and for N-acetyltransferase activity in peripheral blood mononuclear leukocytes (MNL) using p-aminobenzoic acid (PABA). These are markers for systemic NAT2 and NAT1 N-acetyltransferase activities, respectively. Fourteen slow acetylators and four fast acetylators (the NAT2 polymorphism) were identified by the caffeine metabolite ratio. In slow acetylators who have decreased levels of hepatic NAT2, the AFMU/1X ratio was significantly correlated with PABA acetylation in MNL (r = 0.8; p = 0.0002). These results suggest that significant variation in the acetylation of arylamine substrates susceptible to the classical acetylator polymorphism is attributable to variation in NAT1 activity in the slow acetylator phenotype.
Cribb
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AE
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Isbrucker
R
R
Levatte
T
T
Tsui
B
B
Gillespie
C T
CT
Renton
K W
KW
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000107:Acetylation; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers; D002110:Caffeine / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013379:Substrate Specificity; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine; D014970:Xanthines / Q000652:urine
D015415:Biomarkers; D007527:Isoenzymes; D014970:Xanthines; D002110:Caffeine; D014498:Uracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; D010129:4-Aminobenzoic Acid