Most xenobiotic-metabolizing enzymes (XME) affect the bioavailability of drugs, making them important determinants in pharmacogenomics. The arylamine Nacetyltransferases (NATs) are XME that participate in the metabolism of numerous primary arylamines and hydrazine drugs. In addition to their N-acetylation catalytic activity, NAT enzymes have also O-acetylation activity towards N-hydroxyarylamines. The NAT2 phenotype was one of the earliest hereditary traits to be identified that modulate drug metabolism . Based on preliminary observations, drugs such as isoniazid and sulfamethazine were described as “polymorphic” (efficacy different depending on individuals) whereas others, such as p-aminosalicylic acid, were described as “monomorphic”. This dichotomy was due, at least in part, to low levels of the NAT2 isoform in 50-60% of individuals of european descent, these individuals being described as “slow acetylators”. It is now recognized that the human NAT1 and NAT2 loci are highly polymorphic, with more than 25 alleles identified at each locus.
In collaboration with Cedric Werely we investigating the functional consequences of NAT SNPs in South African individuals using and intersection of homology modeling and SNP detection.
For more information on NAT1:
For more information on NAT2: