Nikiforov Andrey, Kulikova Veronika, Ziegler Mathias
a Institute of Nanobiotechnologies, St. Petersburg State Polytechnical University , St. Petersburg , Russia .
b Institute of Cytology, Russian Academy of Sciences , St. Petersburg , Russia , and.
Crit Rev Biochem Mol Biol. 2015;50(4):284-97. doi: 10.3109/10409238.2015.1028612. Epub 2015 Apr 2.
The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD(+) and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools.
NAD的代谢已成为细胞和机体稳态的关键调节因子。作为生物能量和信号通路的主要组成部分，该分子非常适合调节代谢和主要的细胞事件。在人类中，NAD由维生素B3前体合成，最主要的是由烟酰胺合成，烟酰胺是所有NAD依赖性信号反应的降解产物。NAD介导的调节过程范围广泛，包括酶调节、基因表达和健康寿命控制、DNA修复、细胞周期调节和钙信号传导。在这些过程中，烟酰胺从NAD(+)中裂解出来，剩余的ADP-核糖部分用于修饰蛋白质（通过去乙酰化酶进行脱乙酰化或进行ADP-核糖基化）或生成钙动员剂，如环ADP-核糖。本综述还将强调NAD代谢组中中间体的作用、它们在细胞内和细胞外的转化以及对NAD池亚细胞区室化的潜在贡献。
