Introduction

Acetylation catalyzed by the arylamine N-acetyltrans-ferases (NATs; EC 2.3.1.5) is a major biotransformation pathway for arylamine and hydrazine drugs, as well as many carcinogens that we are exposed to on a daily basis found in foodstuffs, cigarette smoke, and the environment. These compounds can either be detoxified (N-acetylation) by NATs and eliminated from the body, or bioactivated (O-acetylation) to metabolites that have the potential to cause toxicity such as cancer. As a result, NAT levels in the body have clinical importance with regard to drug effect and individual susceptibility to toxicity. In humans, these reactions are catalyzed by two closely related, highly polymorphic enzymes (NAT1 and NAT2), which differ in their substrate specificity and tissue distribution. This article focuses on recent advances in the molecular genetics of the human NATs and their clinical implications.

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