Regulation of Arylamine N-Acetyltransferases
Neville J. Butcher, Jacky Tiang and Rodney F. Minchin
Affiliation: School of Biomedical Sciences,University of Queensland, St Lucia QLD 4072, Australia.
Acetylation catalysed by the arylamine N-acetyltransferases (NATs; 220.127.116.11) is a major biotransformation pathway for arylamine and hydrazine drugs, as well as many carcinogens that we are exposed to on a daily basis. These compounds can either be detoxified by NATs or bioactivated to metabolites that have the potential to cause toxicity such as cancer. As a result, the levels of NATs in the body have clinical importance with regard to drug effect and individual susceptibility to toxicity. Like many other drug metabolising enzymes, the activity of NATs varies considerably between individuals, due in part to genetic polymorphisms. However, it is becoming increasingly evident that non-genetic factors also play an important role in regulating NAT activity in vivo. This review focuses on the nongenetic control of NAT expression, including transcriptional, post-transcriptional/translational, and post-translational regulation. In addition, the dysregulation of NAT1 expression in cancer cells is reviewed, as this is an emerging area that may provide insight into a role for NAT1 in cancer biology.
Keywords: Arylamine N-acetyltransferase, regulation, NAT1, NAT2, transcription, promoter, gene expression
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