Hein D W, Trinidad A, Yerokun T, Ferguson R J, Kirlin W G, Weber W W
Department of Pharmacology, Morehouse School of Medicine, Atlanta, GA 30310-1495.
Drug Metab Dispos. 1988 May-Jun;16(3):341-7.
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)
对来自纯合快速乙酰化剂C57BL/6J和A.B6同基因近交小鼠品系、纯合慢速乙酰化剂A/J和B6.A同基因近交小鼠品系以及（C57BL/6J×A/J）F1杂合乙酰化剂杂交小鼠品系的肝脏胞质溶胶中的乙酰辅酶A依赖性N - 乙酰转移酶和O - 乙酰转移酶活性进行了检测。对氨基苯甲酸、2 - 氨基芴和4 - 氨基联苯的N - 乙酰化表现出乙酰化剂基因型依赖性N - 乙酰转移酶活性。相比之下，小鼠肝脏胞质溶胶中异烟肼N - 乙酰转移酶和N - 羟基 - 3,2'-二甲基 - 4 - 氨基联苯O - 乙酰转移酶活性水平似乎与芳胺N - 乙酰化酶基因无关。尽管对于对氨基苯甲酸、2 - 氨基芴和4 - 氨基联苯，亲本C57BL/6J和A/J品系之间的胞质溶胶N - 乙酰转移酶活性相差约2倍，但纯合快速乙酰化剂A.B6和纯合慢速乙酰化剂B6.A同基因近交品系之间相同的N - 乙酰转移酶活性相差约6 - 7倍。对五个近交小鼠品系中乙酰辅酶A依赖性芳胺N - 乙酰转移酶活性的部分纯化显示，在所检测的快速和慢速乙酰化剂小鼠品系的肝脏胞质溶胶中各有一种主要的对氧磷抗性酶。部分纯化的2 - 氨基芴和4 - 氨基联苯N - 乙酰转移酶活性水平在A.B6中比B6.A同基因近交品系高约7倍。乙酰辅酶A依赖性异烟肼N - 乙酰转移酶活性的部分纯化显示，其催化作用由一种不同于主要芳胺N - 乙酰转移酶的对氧磷抗性酶介导。这些结果表明，小鼠肝脏胞质溶胶中的异烟肼N - 乙酰转移酶是一个独立于芳胺N - 乙酰化酶基因分离的单独基因的产物。（摘要截断于250字）
