Relationship between in vivo acetylator phenotypes and cytosolic N-acetyltransferase and O-acetyltransferase activities in human uroepithelial cells.
The in vivo acetylator phenotype as well as N-acetyltransferase (NAT) and O-acetyltransferase (OAT) activities in cytosols from cultured uroepithelia were determined in 25 urological patients. In vivo acetylator phenotypes were categorized by determining the amounts of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine in urine after the administration of a 200 mg dose of caffeine. Subjects were grouped according to the AFMU/AFMU + 1-methylxanthine ratio as "slow" (< 0.41) or "rapid" (> or = 0.41) acetylators. The uroepithelia were obtained from these subjects, cultured in vitro, and the cytosols were prepared. NAT and OAT activities were determined using 4-aminobiphenyl (ABP) and [3H]N-hydroxy-4-aminobiphenyl (N-OH-ABP) as substrates, respectively. In vivo phenotyping resulted in 18 patients being slow acetylators and seven rapid. The mean NAT and OAT activities for these different subsets were: 3.58 nmol/mg protein/min and 409 pmol/mg tRNA/mg protein for the slow; and 3.38 nmol/mg protein/min and 428 pmol/mg tRNA/mg protein for the rapid, respectively. Furthermore, in individual samples, NAT and OAT activities tended to parallel each other, implying that the same enzyme might catalyze both NAT and OAT activities in uroepithelia. The N-acetylation of ABP was inhibited by N-OH-ABP and also by p-aminobenzoic acid, a substrate which is preferred by the monomorphic NAT enzyme. Similarly, OAT-mediated binding of [3H]N-OH-ABP to tRNA was inhibited in a dose-dependent manner by ABP and p-aminobenzoic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Frederickson
S M
SM
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison 53792.
Messing
E M
EM
Reznikoff
C A
CA
Swaminathan
S
S
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D002110:Caffeine / Q000493:pharmacokinetics; D002478:Cells, Cultured; D004848:Epithelium / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013418:Sulfamethazine; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine; D014513:Ureter / Q000201:enzymology*; D001743:Urinary Bladder / Q000201:enzymology*; D014970:Xanthines / Q000652:urine
D014970:Xanthines; D002110:Caffeine; D013418:Sulfamethazine; D014498:Uracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase