Transfer reactions amine acetylating enzyme

The loss of acetyl CoA was found to be caused by a nonenzymatic transfer of acetyl groups to other sulfhydryl compounds added to the system. Ordinarily sulfhydryl compounds should not be required in reactions of acetyl CoA, as opposed to systems using free CoA, whose —SH group needs protection. But the amine-acetylating enzyme also has essential —SH groups that require protection. The dilemma was... 

This enzyme [EC 2.3.1.5], also known as acetyl-CoA arylamine A-acetyltransferase and arylamine acetylase, catalyzes the reaction of acetyl-CoA with an arylamine to produce coenzyme A and an A-acetylarylamine. This enzyme exhibits a low specificity with respect to the aromatic amine substrate. In fact, even serotonin can serve as a substrate. The enzyme has also been reported to catalyze acetyl-transfer reactions between arylamines without the use of coenzyme A. 

Figure 43-1 I Schematic view of the role of NAT enzymes in the metabolism of aromatic amines. N-acetylation might be a detoxification reaction in a number of cases however, after N-hydroxylation of aromatic amines (e.g., by CYP enzymes), NAT enzymes can bioactivate these intermediates by either 0-acetylation or intramolecular N,0-acety transfer, leading to the formation of nitrenium ions, which might react with DNA or alternatively be detoxified by, for example, GST enzymes. Importantly, it is shown that a number of other biotransformation enzymes are also involved in the metabolism of aromatic amines as well. (Redrawn from Wormhoudt LW, Commandeur jNM, Vermeuien NPE. Genetic polymorphisms of human N-acetyitransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes relevance to xenobiotic metabolism and toxicity. Crit Rev Toxicol 1999 29 59-124. Reproduced by permission from Taylor and Francis, Inc.)...

This enzyme catalyses reactions with many aromatic amines including serotonin. It can also catalyse acetyl transfer between arylamines without CoA. 

Acetylation of amines is an important route for the metabolism of primary aromatic amines such as the sul-phonamide dmgs or the antituberculosis dmg isoniazid (Fig. 3.22). The co-factor involved in acetate transfer is acetyl co-enzyme A (acetyl CoA) and the reaction is catalysed by acetyl transferase, N-acetylation generally reduces toxicity. 

---