KINETICS OF ACETYL-COENZYME A-ARYLAMINE N-ACETYLTRANSFERASE FROM RAPID AND SLOW ACETYLATOR FROG TISSUES

Citation
Cc. Ho et al., KINETICS OF ACETYL-COENZYME A-ARYLAMINE N-ACETYLTRANSFERASE FROM RAPID AND SLOW ACETYLATOR FROG TISSUES, Drug metabolism and disposition, 24(2), 1996, pp. 137-141
Citations number
27
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00909556
Volume
24
Issue
2
Year of publication
1996
Pages
137 - 141
Database
ISI
SICI code
0090-9556(1996)24:2<137:KOAANF>2.0.ZU;2-F
Abstract
N-acetyltransferase (NAT) activity was determined in 100 frog (Rana li grina) livers using 2-aminofluorene and p-aminobenzoic acid as substra tes. Overall, the liver NAT activity of the 50 females was higher than the liver NAT activity of the 50 males. The activities (mean +/- SD) of NAT from the bladder, blood, colon, and liver of males was 0.30 +/- 0.11, 0.05 +/- 0.03, 0.09 +/- 0.05, and 0.93 +/- 0.56 nmol/min/mg pro tein for the acetylation of aminofluorene and 0.29 +/- 0.06, 0.36 +/- 0.04, 0.26 +/- 0.02, and 0.32 +/- 0.14 nmol/min/mg protein for the ace tylation of p-aminobenzoic acid. In the bladder, blood, colon, and liv er from female frogs, the activities obtained were 1.00 +/- 0.41,0.52 +/- 0.07, 0.08 +/- 0.05, and 1.27 +/- 0.49 nmol/min/mg protein for ami nofluorene and 0.34 +/- 0.12, 0.36 +/- 0.04, 0.34 +/- 0.07, and 0.48 /- 0.21 nmol/min/mg protein for p-aminobenzoic acid. Kinetic constants for arylamine NAT activity in the blood, liver, bladder, and colon fr om frogs with rapid, intermediate, and slow acetylator activities were determined. K-M and V-max values for aminofluorene were 2- to 6-fold higher for liver than for the other tissues. K-M and V-max values for p-aminobenzoic acid showed a smaller variation among the tissues exami ned, with values obtained for the liver and bladder being somewhat hig her than the values for the blood and colon. An apparent K-M differenc e for aminofluorene was found in the liver from frogs with high and lo w acetylator activity. Based on the aminofluorene NAT activity of live r, there seems to be a polymorphism in NAT activity with 4 rapid, 21 i ntermediate, and 75 slow acetylators among the 100 frogs assayed. Dist ribution of acetylator phenotypes was similar among the 50 males and 5 0 females in this study. This is the first demonstration of acetyl coe nzyme A:arylamine NAT activity in an amphibian and could lead to the d evelopment of a frog model for monitoring the effect of pollution of w etland environments on native species.