Genetic control of acetyl coenzyme A-dependent arylamine N-acetyltransferase, hydrazine N-acetyltransferase, and N-hydroxy-arylamine O-acetyltransferase enzymes in C57BL/6J, A/J, AC57F1, and the rapid and slow acetylator A.B6 and B6.A congenic inbred mouse.
Acetyl coenzyme A-dependent N-acetyltransferase and O-acetyltransferase activities were examined in liver cytosols derived from homozygous rapid acetylator C57BL/6J and A.B6 congenic inbred mouse strains, from homozygous slow acetylator A/J and B6.A congenic inbred mouse strains, and from the (C57BL/6J x A/J)F1 heterozygous acetylator hybrid mouse strain. Acetylator genotype-dependent N-acetyltransferase activity was exhibited for the N-acetylation of p-aminobenzoic acid, 2-aminofluorene, and 4-aminobiphenyl. In contrast, levels of isoniazid N-acetyltransferase and N-hydroxy-3,2'-dimethyl-4-aminobiphenyl O-acetyltransferase activities in mouse liver cytosol appeared to be independent of the arylamine Nat acetylator gene. Although cytosolic N-acetyltransferase activities differed about 2-fold between the parental C57BL/6J and A/J strains for p-aminobenzoic acid, 2-aminofluorene, and 4-aminobiphenyl, the same N-acetyltransferase activities differed about 6-7-fold between the homozygous rapid acetylator A.B6 and the homozygous slow acetylator B6.A congenic inbred strains. Partial purification of acetyl coenzyme A-dependent arylamine N-acetyltransferase activity in the five inbred mouse strains showed one major paraoxon-resistant enzyme in liver cytosol in each of the rapid and slow acetylator mouse strains examined. Levels of partially purified 2-aminofluorene and 4-aminobiphenyl N-acetyltransferase activity were about 7-fold higher in the A.B6 than the B6.A congenic inbred strain. Partial purification of acetyl coenzyme A-dependent isoniazid N-acetyltransferase activity showed catalysis by a paraoxon-resistant enzyme(s) distinct from the major arylamine N-acetyltransferase enzyme(s). These results suggest that isoniazid N-acetyltransferase(s) in mouse liver cytosol is a product of a separate gene that segregates independently of the arylamine Nat gene.(ABSTRACT TRUNCATED AT 250 WORDS)
D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism*; D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000201:enzymology; D005838:Genotype; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010261:Paraoxon / Q000494:pharmacology; D013045:Species Specificity
D000217:Acyltransferases; D000123:Acetyltransferases; C019736:N-hydroxyarylamine O-acetyltransferase; D001191:Arylamine N-Acetyltransferase; D000101:Acetyl-CoA C-Acetyltransferase; D010261:Paraoxon