Nacetyltransferase

N-acetyltransferase is an enzyme that catalyzes the transfer of an acetyl group from acetyl-CoA to an amino substrate, typically forming an N-acetylamide. N-acetyltransferases are found in a wide range of organisms, including bacteria, plants, and animals, and many share a common structural framework known as the GNAT (GCN5-related N-acetyltransferase) superfamily. The family encompasses enzymes with diverse biological roles but a conserved mechanism for acetyl group transfer.

The primary reaction involves acetyl-CoA as the acetyl donor and an amine-containing substrate as the acceptor, yielding CoA and the N-acetylated product. Substrates can include arylamines, hydrazines, and various amines; some NATs acetylate small molecule xenobiotics, while others participate in endogenous processes such as hormone and pigment biosynthesis. Notable examples include bacterial aminoglycoside N-acetyltransferases that inactivate antibiotics, and arylalkylamine N-acetyltransferases involved in melatonin production in animals.

In humans, two major cytosolic NAT enzymes are NAT1 and NAT2, encoded by separate genes. These enzymes metabolize a variety of drugs and environmental arylamines. Genetic polymorphisms in NAT2, in particular, give rise to fast and slow acetylator phenotypes, influencing drug clearance, toxicity risk, and susceptibility to certain cancers linked to arylamine exposure. Similar enzymes participate in plant and bacterial metabolism, contributing to secondary metabolite formation or antibiotic resistance.

Structurally, NATs typically adopt a compact GNAT fold of around 140–200 amino acids and use acetyl-CoA binding to position the acetyl group for transfer to the substrate’s amino nitrogen. The enzymes display considerable functional diversity, reflecting adaptation to different physiological and ecological contexts.