The human NAD metabolome: Functions, metabolism and compartmentalization

• Published in: Critical reviews in biochemistry and molecular biology Vol. 50; no. 4; pp. 284 - 297
• Main Authors: Nikiforov, Andrey, Kulikova, Veronika, Ziegler, Mathias
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 04.07.2015
• Subjects: ADP-ribosylation; Animals; calcium signaling; Energy Metabolism; extracellular NAD degradation; Humans; Metabolome; Models, Biological; NAD - metabolism; NAD biosynthesis; Organelles - enzymology; Organelles - metabolism; protein deacetylation; Review; Signal Transduction; subcellular NAD pools; subcellular NAD pools; protein deacetylation; NAD biosynthesis; extracellular NAD degradation; calcium signaling; ADP-ribosylation
• ISSN: 1040-9238; 1549-7798
• DOI: 10.3109/10409238.2015.1028612

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.