Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression.

摘要: N-Acetylation by hepatic arylamine N-acetyltransferase (NAT, EC 2.3.1.5) is a major route in the metabolism and detoxification of numerous drugs foreign chemicals. NAT target common genetic polymorphism clinical relevance human populations. We have used our recently isolated rabbit cDNA rnat to clone three genes from leukocyte DNA. None genomic coding sequences was interrupted introns. Two genes, designated NAT1 NAT2, each possessed open reading frames 870 bp. Both been assigned chromosome 8, pter-q11. Following transfection they were transiently expressed monkey kidney COS-1 cells. NAT2 gave rise functional proteins, as judged their enzyme activity with substrate sulfamethazine. Western blots NAT-specific antisera detected proteins apparent molecular weight 33 31 kD NAT1- NAT2-transfected cultures, respectively. The product had an identical that liver cytosol. deduced amino acid sequence also contained 6 peptide which previously determined tryptic peptides polymorphic purified liver. These data suggest encodes protein. third gene, NATP, multiple deleterious mutations did not encode protein; it most likely represents pseudogene.