PathwayStep2725 PathwayStep2724 PathwayStep2723 PathwayStep2726 Acetylation Authored: Jassal, B, 2004-11-30 16:21:24 Edited: Jassal, B, 2008-05-19 12:57:01 N-acetyltransferases (NATs; EC 2.3.1.5) utilize acetyl Co-A in acetylation conjugation reactions. This is the preferred route of conjugating aromatic amines (R-NH2, converted to aromatic amides R-NH-COCH3) and hydrazines (R-NH-NH2, converted to R-NH-NH-COCH3). Aliphatic amines are not substrates for NAT. The basic reaction is<br><p><b>Acetyl-CoA + an arylamine = CoA + an N- acetylarylamine</b></p><br>NATs are cytosolic and in humans, 2 isoforms are expressed, NAT1 and NAT2. A third isoform, NATP, is a pseudogene and is not expressed. The NAT2 gene contains mutations that decrease NAT2 activity. This mutations was first seen as <i>slow acetylation</i> compared to the normal, <i>fast acetylation</i> of the antituberculosis drug isoniazid. Incidence of the slow acetylator phenotype is high in Middle Eastern populations (70%), average (50%) in Europeans, Americans and Australians and low in Asians (<25% in Chinese, Japanese and Koreans). N-acetylation and methylation pathways differ from other conjugation pathways in that they mask an amine with a nonionizable group so that the conjugates are less water soluble than the parent compound. However, certain N-acetlylations facilitate urinary excretion.<br>N-acetylation occurs in two sequential steps via a <i>ping-pong Bi-Bi mechanism</i>. In the first step, the acetyl group from acetyl-CoA is transferred to a cysteine residue in NAT, with consequent release of coenzyme-A. In the second step, the acetyl group is released from the acetylated NAT to the substrate, subsequently regenerating the enzyme. Pubmed12052143 Pubmed1559981 Pubmed2340091 Reactome Database ID Release 43156582 Reactome, http://www.reactome.org ReactomeREACT_6732 NAT2 acetylation The acetyl group from acetyl-CoA is transferred to the NAT2 NAT1 acetylation The acetyl group from acetyl-CoA is transferred to the NAT1