Department of Anesthesiology, University of Rochester Medical Center, Rochester, New York.
Antioxid Redox Signal. 2019 Sep 20;31(9):623-642. doi: 10.1089/ars.2018.7722. Epub 2019 Mar 26.
Nicotinamide adenine dinucleotide (NAD) spans diverse roles in biology, serving as both an important redox cofactor in metabolism and a substrate for signaling enzymes that regulate protein post-translational modifications (PTMs). Although the interactions between these different roles of NAD (and its reduced form NADH) have been considered, little attention has been paid to the role of compartmentation in these processes. Specifically, the role of NAD in metabolism is compartment specific (, mitochondrial cytosolic), affording a very different redox landscape for PTM-modulating enzymes such as sirtuins and poly(ADP-ribose) polymerases in different cell compartments. In addition, the orders of magnitude differences in expression levels between NAD-dependent enzymes are often not considered when assuming the effects of bulk changes in NAD levels on their relative activities. In this review, we discuss the metabolic, nonmetabolic, redox, and enzyme substrate roles of cellular NAD, and the recent discoveries regarding the interplay between these roles in different cell compartments. Therapeutic implications for the compartmentation and manipulation of NAD biology are discussed. 31, 623-642.
烟酰胺腺嘌呤二核苷酸（NAD）在生物学中具有多种作用，既是代谢中重要的氧化还原辅酶，也是调节蛋白质翻译后修饰（PTMs）的信号酶的底物。尽管已经考虑了 NAD（及其还原形式 NADH）的这些不同作用之间的相互作用，但对这些过程中隔室化的作用关注甚少。具体而言，NAD 在代谢中的作用是隔室特异性的（线粒体、细胞质），为不同细胞隔室中的 sirtuins 和聚（ADP-核糖）聚合酶等调节 PTM 的酶提供了非常不同的氧化还原景观。此外，当假设 NAD 水平的总体变化对其相对活性的影响时，通常不考虑 NAD 依赖性酶之间表达水平的数量级差异。在这篇综述中，我们讨论了细胞 NAD 的代谢、非代谢、氧化还原和酶底物作用，以及关于这些作用在不同细胞隔室中的相互作用的最新发现。讨论了 NAD 生物学的隔室化和操纵的治疗意义。 31, 623-642.
