Butcher Neville J, Tiang Jacky, Minchin Rodney F
School of Biomedical Sciences, University of Queensland, St Lucia QLD 4072, Australia.
Curr Drug Metab. 2008 Jul;9(6):498-504. doi: 10.2174/138920008784892128.
Acetylation catalysed by the arylamine N-acetyltransferases (NATs; 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. 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 non-genetic 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.
芳胺N-乙酰基转移酶（NATs；2.3.1.5）催化的乙酰化作用是芳胺和肼类药物以及我们日常接触的许多致癌物的主要生物转化途径。这些化合物既可以被NATs解毒，也可以被生物激活为具有致癌等潜在毒性的代谢产物。因此，体内NATs的水平在药物疗效和个体对毒性的易感性方面具有临床重要性。与许多其他药物代谢酶一样，NATs的活性在个体之间差异很大，部分原因是基因多态性。然而，越来越明显的是，非遗传因素在体内调节NAT活性方面也起着重要作用。本综述重点关注NAT表达的非遗传控制，包括转录、转录后/翻译和翻译后调控。此外，还综述了癌细胞中NAT1表达的失调情况，因为这是一个新兴领域，可能为了解NAT1在癌症生物学中的作用提供线索。
