Hein D W, Smolen T N, Fox R R, Weber W W
J Pharmacol Exp Ther. 1982 Oct;223(1):40-4.
Liver and gut mucosa N-acetyltransferase (NAT) cytosol (105,000 x g) was prepared from selected lines of New Zealand White rapid and slow acetylator rabbits bred and housed at the University of Michigan, and from inbred and partially inbred rabbits obtained from The Jackson Laboratory. Liver NAT activity was determined with p-aminobenzoic acid, p-aminosalicyclic acid, procainamide, sulfamethazine, isoniazid and 2-aminofluorene as substrates. Gut mucosal NAT activity was determined with 2-aminofluorene. A gene dose-response relationship was observed for both liver NAT and gut mucosa NAT with all substrates tested. Highest levels were always observed in homozygous rapid acetylator inbred strains (B/J, III/J, IIIC/J, III/DwJ, IIIEP/J and IIIVO/J), lower levels in obligate heterozygous rapid acetylator rabbits and lowest levels in homozygous slow acetylator inbred (ACEP/J, III/cdJ, IIIVO/ahJ, and IIIVO/vptJ) and outbred rabbits. The differences in magnitude of liver NAT activity level between acetylator genotypes was dependent on the substrate employed, progressively increasing in the following order: p-aminobenzoic acid, p-aminosalicyclic acid, procainamide, sulfamethazine, isoniazid, 2-aminofluorene. The determination of kinetic constants for liver p-aminosalicyclic acid NAT activity indicated a 2-fold difference in apparent Vmax between rapid acetylator genotypes and a 30-fold difference between rapid and slow acetylator phenotypes. In addition, the apparent Km for p-aminosalicyclic acid was significantly lower in the slow acetylators than in the rapid acetylators.
从密歇根大学饲养的新西兰白兔快速和慢速乙酰化品系，以及从杰克逊实验室获得的近交和部分近交兔中，制备肝脏和肠道黏膜N - 乙酰转移酶（NAT）胞质溶胶（105,000×g）。以对氨基苯甲酸、对氨基水杨酸、普鲁卡因酰胺、磺胺二甲嘧啶、异烟肼和2 - 氨基芴为底物测定肝脏NAT活性。以2 - 氨基芴为底物测定肠道黏膜NAT活性。在所有测试底物中，均观察到肝脏NAT和肠道黏膜NAT的基因剂量反应关系。在纯合快速乙酰化近交品系（B/J、III/J、IIIC/J、IIIV/DwJ、IIIEP/J和IIIV0/J）中总是观察到最高水平，在 obligate 杂合快速乙酰化兔中水平较低，在纯合慢速乙酰化近交（ACEP/J、III/cdJ、IIIV0/ahJ和IIIV0/vptJ）和远交兔中水平最低。乙酰化基因型之间肝脏NAT活性水平的差异幅度取决于所使用的底物，按以下顺序逐渐增加：对氨基苯甲酸、对氨基水杨酸、普鲁卡因酰胺、磺胺二甲嘧啶、异烟肼、2 - 氨基芴。肝脏对氨基水杨酸NAT活性动力学常数的测定表明，快速乙酰化基因型之间的表观Vmax有2倍差异，快速和慢速乙酰化表型之间有30倍差异。此外，慢速乙酰化剂中对氨基水杨酸的表观Km明显低于快速乙酰化剂。
