Arylamine N-acetyltransferase (NAT) (NAT)

Arylamine N-acetyltransferases (NATs) are essential Phase II metabolic enzymes that catalyze the acetylation of various drugs and environmental toxins. In humans, the family consists of two primary functional isoforms, NAT1 and NAT2, which are characterized by significant genetic variability. NAT2 is predominantly expressed in the liver and is the primary enzyme responsible for the metabolism of several important therapeutic agents, including the anti-tuberculosis drug isoniazid and various sulfonamides (StatPearls, NBK557546). Genetic polymorphisms in the NAT2 gene result in distinct "slow," "intermediate," and "rapid" acetylator phenotypes, which directly impact drug clearance and the likelihood of adverse drug reactions (UniProt, P11245). Slow acetylators are particularly susceptible to drug-induced toxicities, such as peripheral neuropathy and hepatotoxicity, due to the accumulation of parent compounds or alternative toxic metabolites. Furthermore, NAT enzymes are involved in the activation of pro-carcinogens, linking specific acetylator phenotypes to an increased risk of bladder and colorectal cancers (PubMed, 18419308). NAT1, while more ubiquitously expressed, also contributes to the metabolism of both endogenous and exogenous arylamines, making the entire NAT family a critical consideration in pharmacogenetics and personalized medicine.

Other names

NAT1NAT2Arylamine acetylaseN-acetyltransferase 1N-acetyltransferase 2

Catalyzes the transfer of an acetyl group from acetyl-CoA to the nitrogen atom of primary arylamine, hydrazine, or hydrazide substrates (N-acetylation) or the oxygen atom of N-hydroxylated metabolites (O-acetylation).