Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27701, United States; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, United States.
Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Biochim Biophys Acta Bioenerg. 2017 Dec;1858(12):991-998. doi: 10.1016/j.bbabio.2017.09.005. Epub 2017 Sep 22.
NAD is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD, NADH, and the NAD/NADH ratio have long been known to control the activity of several oxidoreductase enzymes. More recently, enzymes outside those participating directly in redox control have been identified that sense these dinucleotides, including the sirtuin family of NAD-dependent protein deacylases. In this review, we highlight examples of non-redox enzymes that are controlled by NAD, NADH, or NAD/NADH. In particular, we focus on the sirtuin family and assess the current evidence that the sirtuin enzymes sense these dinucleotides and discuss the biological conditions under which this might occur; we conclude that sirtuins sense NAD, but neither NADH nor the ratio. Finally, we identify future studies that might be informative to further interrogate physiological and pathophysiological changes in NAD and NADH, as well as enzymes like sirtuins that sense and respond to redox changes in the cell.
NAD 是一种二核苷酸辅因子，具有在多种细胞氧化还原（redox）反应中接受电子的潜力。在其还原形式中，NADH 是一种普遍存在的细胞电子供体。NAD、NADH 和 NAD/NADH 比值长期以来一直被认为可以控制几种氧化还原酶的活性。最近，已经鉴定出了一些不在直接参与氧化还原控制的酶，这些酶可以感知这些二核苷酸，包括 NAD 依赖性蛋白去乙酰化酶的 Sirtuin 家族。在这篇综述中，我们强调了受 NAD、NADH 或 NAD/NADH 控制的非氧化还原酶的例子。特别是，我们专注于 Sirtuin 家族，并评估了当前关于 Sirtuin 酶感知这些二核苷酸的证据，并讨论了可能发生这种情况的生物学条件；我们得出结论，Sirtuin 感知 NAD，但不感知 NADH 或 NAD/NADH 比值。最后，我们确定了未来的研究方向，这些研究可能有助于进一步探究 NAD 和 NADH 以及像 Sirtuin 这样感知和响应细胞内氧化还原变化的酶的生理和病理生理学变化。
