Kulikova V A, Gromyko D V, Nikiforov A A
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
Peter the Great St. Petersburg Polytechnic University, St. Petersburg, 195251, Russia.
Biochemistry (Mosc). 2018 Jul;83(7):800-812. doi: 10.1134/S0006297918070040.
Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form NADP are the major coenzymes in the redox reactions of various essential metabolic pathways. NAD+ also serves as a substrate for several families of regulatory proteins, such as protein deacetylases (sirtuins), ADP-ribosyltransferases, and poly(ADP-ribose) polymerases, that control vital cell processes including gene expression, DNA repair, apoptosis, mitochondrial biogenesis, unfolded protein response, and many others. NAD+ is also a precursor for calcium-mobilizing secondary messengers. Proper regulation of these NAD-dependent metabolic and signaling pathways depends on how efficiently cells can maintain their NAD levels. Generally, mammalian cells regulate their NAD supply through biosynthesis from the precursors delivered with the diet: nicotinamide and nicotinic acid (vitamin B3), as well as nicotinamide riboside and nicotinic acid riboside. Administration of NAD precursors has been demonstrated to restore NAD levels in tissues (i.e., to produce beneficial therapeutic effects) in preclinical models of various diseases, such as neurodegenerative disorders, obesity, diabetes, and metabolic syndrome.
烟酰胺腺嘌呤二核苷酸（NAD）及其磷酸化形式NADP是各种重要代谢途径氧化还原反应中的主要辅酶。NAD+还是几类调节蛋白的底物，如蛋白质脱乙酰酶（沉默调节蛋白）、ADP核糖基转移酶和聚（ADP-核糖）聚合酶，这些蛋白控制着包括基因表达、DNA修复、细胞凋亡、线粒体生物发生、未折叠蛋白反应等在内的重要细胞过程。NAD+也是钙动员第二信使的前体。这些依赖NAD的代谢和信号通路的适当调节取决于细胞维持其NAD水平的效率。一般来说，哺乳动物细胞通过从饮食中摄入的前体物质进行生物合成来调节其NAD供应：烟酰胺和烟酸（维生素B3），以及烟酰胺核糖和烟酸核糖。在各种疾病的临床前模型中，如神经退行性疾病、肥胖、糖尿病和代谢综合征，已证明给予NAD前体可恢复组织中的NAD水平（即产生有益的治疗效果）。
