N-acetyltransferase (NAT)

N-acetyltransferases (NATs) are a family of cytosolic enzymes that catalyze the transfer of acetyl groups from acetyl-CoA to arylamines, arylhydroxylamines, and arylhydrazines, contributing to the biotransformation and detoxification of a wide range of drugs and environmental chemicals (xenobiotics)[1][2]. The two primary human isoforms, N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2), differ in substrate specificity and tissue distribution[1]. NAT2 is well-known in pharmacogenetics because its genetic polymorphisms result in different acetylator phenotypes, which impact individual susceptibility to drug toxicity and some cancers, especially when exposed to aromatic and heterocyclic amines (such as those in cigarette smoke and certain drugs)[1][2]. Variants in NAT genes have also been genetically associated with insulin resistance and possibly diabetes[1]. In addition to drug metabolism, specific NAT enzymes (such as arylalkylamine N-acetyltransferase in the brain) are crucial for the synthesis of important neurotransmitters like melatonin, showing additional roles in circadian rhythm regulation[3]. Due to its diversity and the existence of multiple homologs and pseudogenes, "N-acetyltransferase" should be specified by isoenzyme (such as NAT1, NAT2, or aaNAT) for precise targeting and clinical interpretation[1][2][3].

Other names

arylamine N-acetyltransferasearylalkylamine N-acetyltransferase (aaNAT)NAT1NAT2GNAT (GCN5-related N-acetyltransferase)acetyltransferasetimezyme (for aaNAT in circadian function)

Acetylation/inactivation of drugs and xenobiotics (phase II metabolism); Modulation of drug and metabolite toxicity; Metabolism of endogenous amines and hormones (e.g., melatonin from serotonin via aaNAT)