AUTHOR=Habil Mariam R. , Doll Mark A. , Hein David W. 

TITLE=Acetyl coenzyme A kinetic studies on N-acetylation of environmental carcinogens by human N-acetyltransferase 1 and its NAT1*14B variant

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.931323

DOI=10.3389/fphar.2022.931323

ISSN=1663-9812

ABSTRACT=<p>N-acetyltransferase 1 (NAT1) is a xenobiotic metabolizing enzyme that uses acetyl coenzyme A (AcCoA) as a cofactor for <italic>N</italic>-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 <italic>NAT1*4</italic> (reference allele) or <italic>NAT1*14B</italic> (variant allele) to measure AcCoA kinetic parameters for <italic>N</italic>-acetyltransferase activity measurements towards <italic>p</italic>-aminobenzoic acid (PABA), 4-aminobiphenyl (4-ABP), β-naphthylamine (BNA), benzidine and 3,4-dimethylaniline (3,4-DMA). Our results showed higher <italic>N</italic>-acetylation rates for each substrate catalyzed by <italic>NAT1*4</italic> compared to <italic>NAT1*14B</italic>. <italic>NAT1*4</italic> exhibited higher affinity to AcCoA when catalyzing the <italic>N</italic>-acetylation of BNA and benzidine compared to <italic>NAT1*14B</italic>. The results of the current study provide further insights into differences in carcinogen metabolism among individuals possessing the <italic>NAT1*14B</italic> haplotype.</p>