In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes (NAT1 and NAT2) as well as one pseudogene, all of which are located together on chromosome 8. Although they were first identified by their role in the acetylation of drugs and other xenobiotics, recent studies have shown strong associations for both enzymes in a variety of diseases, including cancer, cardiovascular disease, and diabetes. There is growing evidence that this association may be causal. Consistently, NAT1 and NAT2 are shown to be required for healthy mitochondria. This review discusses the current literature on the role of both NAT1 and NAT2 in mitochondrial bioenergetics. It will attempt to relate our understanding of the evolution of the two genes with biologic function and then present evidence that several major metabolic diseases are influenced by NAT1 and NAT2. Finally, it will discuss current and future approaches to inhibit or enhance NAT1 and NAT2 activity/expression using small-molecule drugs.

中文翻译：

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芳胺 N-乙酰转移酶作为线粒体功能障碍相关代谢性疾病的治疗靶点


在人类中，有两个编码功能性酶（ NAT1和NAT2 ）的芳基胺 N-乙酰转移酶基因以及一个假基因，所有这些基因都一起位于 8 号染色体上。与其他外源物质一样，最近的研究表明，这两种酶与多种疾病密切相关，包括癌症、心血管疾病和糖尿病。越来越多的证据表明这种关联可能是因果关系。一致地，NAT1 和 NAT2 被证明是健康线粒体所必需的。本综述讨论了有关 NAT1 和 NAT2 在线粒体生物能学中的作用的最新文献。它将尝试将我们对这两个基因进化的理解与生物学功能联系起来，然后提供一些主要代谢疾病受 NAT1 和 NAT2 影响的证据。最后，它将讨论当前和未来使用小分子药物抑制或增强 NAT1 和 NAT2 活性/表达的方法。