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Crit Rev Biochem Mol Biol. 2015;50(4):284-97. doi: 10.3109/10409238.2015.1028612. Epub 2015 Apr 2.

The human NAD metabolome: Functions, metabolism and compartmentalization.

Author information

1
a Institute of Nanobiotechnologies, St. Petersburg State Polytechnical University , St. Petersburg , Russia .
2
b Institute of Cytology, Russian Academy of Sciences , St. Petersburg , Russia , and.
3
c Department of Molecular Biology , University of Bergen , Bergen , Norway.

Abstract

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.

KEYWORDS:

ADP-ribosylation; NAD biosynthesis; calcium signaling; extracellular NAD degradation; protein deacetylation; subcellular NAD pools

PMID:
25837229
PMCID:
PMC4673589
DOI:
10.3109/10409238.2015.1028612
[Indexed for MEDLINE]
Free PMC Article

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