Arylamine N-acetyltransferase (NAT (used for family; NAT1 and NAT2 for isoforms))

Arylamine N-acetyltransferases (NATs) are a family of cytosolic transferase enzymes responsible for the acetylation of arylamine, arylhydrazine, and N-hydroxyarylamine substrates, mainly as part of phase II drug metabolism and xenobiotic detoxification[1][2][5]. In humans, two functional isoforms—NAT1 and NAT2—exist, differing in substrate specificity and tissue distribution. NAT2, in particular, plays a critical role in the inactivation of drugs such as isoniazid (for tuberculosis), sulfamethazine, and other primary arylamine therapeutics, with genetic variation (polymorphism) leading to marked interindividual differences in drug response and adverse effects[2][7]. Both isoforms also contribute to the metabolic activation of pro-carcinogens and may participate in endogenous metabolic pathways, such as folate degradation[1][5]. NAT1 is often overexpressed in certain cancers, suggesting additional regulatory or pathogenic roles. Enzymatic activity relies on a conserved catalytic triad, and structural data supports both endogenous and xenobiotic substrate adaptability[3]. NATs are clinically significant pharmacogenetic targets, affecting drug efficacy and toxicity, particularly for isoniazid and hydralazine, and their polymorphisms are important biomarkers for personalized medicine[2][5][7].

Other names

NATArylamide acetylaseN-acetyltransferase type 1N-acetyltransferase type 2NAT1NAT2N-hydroxyarylamine O-acetyltransferasePolymorphic arylamine N-acetyltransferase

Drug inactivation via N-acetylation (e.g., isoniazid); Drug activation (bioactivation of pro-carcinogens into reactive intermediates); Detoxification via O-acetylation (e.g., N-hydroxy metabolites of aromatic amines)