Habil Mariam R, Doll Mark A, Hein David W
Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY, United States.
Front Pharmacol. 2022 Oct 28;13:931323. doi: 10.3389/fphar.2022.931323. eCollection 2022.
N-acetyltransferase 1 (NAT1) is a xenobiotic metabolizing enzyme that uses acetyl coenzyme A (AcCoA) as a cofactor for -acetylation of many carcinogens including aromatic amines and alkylanilines. NAT1 is characterized by single nucleotide polymorphisms (SNPs) that may modulate affinity towards AcCoA. In the current study, we used Chinese hamster ovary (CHO) cells stably transfected with human (reference allele) or (variant allele) to measure AcCoA kinetic parameters for -acetyltransferase activity measurements towards -aminobenzoic acid (PABA), 4-aminobiphenyl (4-ABP), β-naphthylamine (BNA), benzidine and 3,4-dimethylaniline (3,4-DMA). Our results showed higher -acetylation rates for each substrate catalyzed by compared to . exhibited higher affinity to AcCoA when catalyzing the -acetylation of BNA and benzidine compared to . The results of the current study provide further insights into differences in carcinogen metabolism among individuals possessing the haplotype.
N-乙酰基转移酶1（NAT1）是一种外源性物质代谢酶，它利用乙酰辅酶A（AcCoA）作为辅因子，对包括芳香胺和烷基苯胺在内的许多致癌物进行N-乙酰化。NAT1的特征在于单核苷酸多态性（SNP），这些多态性可能会调节其对AcCoA的亲和力。在本研究中，我们使用稳定转染了人野生型（参考等位基因）或突变型（变异等位基因）的中国仓鼠卵巢（CHO）细胞，来测量针对对氨基苯甲酸（PABA）、4-氨基联苯（4-ABP）、β-萘胺（BNA）、联苯胺和3,4-二甲基苯胺（3,4-DMA）的N-乙酰转移酶活性的AcCoA动力学参数。我们的结果表明，与野生型相比，突变型催化的每种底物的N-乙酰化速率更高。与野生型相比，突变型在催化BNA和联苯胺的N-乙酰化时对AcCoA表现出更高的亲和力。本研究结果为具有突变型单倍型的个体之间致癌物代谢差异提供了进一步的见解。
