Cribb A E, Grant D M, Miller M A, Spielberg S P
Department of Pharmacology, University of Toronto, Ontario, Canada.
J Pharmacol Exp Ther. 1991 Dec;259(3):1241-6.
The expression of arylamine N-acetyltransferase (NAT) in leukocytes was investigated using p-aminobenzoic acid (PABA) and sulfamethazine (SMZ), substrates which are preferentially acetylated by the monomorphic NAT1 and polymorphic NAT2 enzymes, respectively. Activity towards both substrates was detected in mononuclear leukocytes (MNL; preparation containing approximately 80% lymphocytes), monocytes and neutrophils. PABA and SMZ acetylation rates were highly correlated in each of the isolated cell types. The NAT in leukocytes displayed a much higher affinity and turnover rate for the acetylation of PABA than for SMZ. These kinetic characteristics suggest that the acetylating activity in human leukocytes is predominantly attributable to the monomorphic enzyme NAT1. Neutrophils showed evidence of biphasic kinetics for SMZ which would indicate the coexpression of NAT1 and low levels of the polymorphic enzyme, NAT2. NAT activity in MNL was not influenced by the acetylator phenotype of the individual. There was, however, a significant correlation between NAT activity in MNL and the in vivo acetylation (urinary metabolite ratio) of p-aminosalicylic acid, which is monomorphically acetylated in humans. The expression of NAT1 in leukocytes and the virtuall absence of NAT2 may have important toxicological implications. The in vitro/in vivo correlation suggests that leukocytes may be a useful marker of systemic NAT1 activity.
使用对氨基苯甲酸（PABA）和磺胺二甲嘧啶（SMZ）研究白细胞中芳胺N - 乙酰基转移酶（NAT）的表达，这两种底物分别优先被单态性NAT1和多态性NAT2酶乙酰化。在单核白细胞（MNL；约含80%淋巴细胞的制剂）、单核细胞和中性粒细胞中均检测到对这两种底物的活性。在每种分离的细胞类型中，PABA和SMZ的乙酰化率高度相关。白细胞中的NAT对PABA乙酰化的亲和力和周转率比对SMZ的要高得多。这些动力学特征表明，人类白细胞中的乙酰化活性主要归因于单态性酶NAT1。中性粒细胞显示出SMZ的双相动力学证据，这表明NAT1和低水平的多态性酶NAT2共同表达。MNL中的NAT活性不受个体乙酰化表型的影响。然而，MNL中的NAT活性与对氨基水杨酸的体内乙酰化（尿代谢物比率）之间存在显著相关性，对氨基水杨酸在人类中是单态性乙酰化的。白细胞中NAT1的表达以及NAT2的几乎不存在可能具有重要的毒理学意义。体外/体内相关性表明，白细胞可能是全身NAT1活性的有用标志物。
