Pharmacogenetics, Regulation and Structural Properties of the Drugmetabolizing Enzymes Arylamine N-acetyltransferases

Xenobiotic-metabolizing enzymes (XME) are responsible for the biotransformation of a vast range of compounds. Arylamine N-acetyltransferases (NAT) are XME responsible for the acetylation of many arylamine and heterocyclic amines. They therefore, play an important role in the detoxification and activation of numerous drugs and carcinogens. Two closely related isoforms (NAT1 and NAT2) have been described in humans. NAT2 is present mainly in the liver and gut whereas NAT1 is found in a wide range of tissues. Interindividual variations in NAT genes have been shown to be a potential source of pharmacological and / or pathological susceptibility. In addition, there is now evidence that non genetic factors, such as substrate-dependent inhibition or redox conditions, may also contribute to overall NAT1 activity. This mini-review summarizes current knowledge on human NATs. Recent aspects of NAT gene expression, regulation and structural properties are discussed.