Format

Send to

Choose Destination
Biochim Biophys Acta. 2016 Dec;1864(12):1787-1800. doi: 10.1016/j.bbapap.2016.06.014. Epub 2016 Jun 29.

NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.

Author information

1
Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
2
Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: aas2004@med.cornell.edu.

Abstract

We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD+ and NADP+ which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD+ has become reinvigorated by new understandings that dynamics within NAD+ metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD+ as an effector substrate. Cellular adaptations include stimulation of mitochondrial biogenesis, a process fundamental to adjusting cellular and tissue physiology to reduced nutrient availability and/or increased energy demand. Several mammalian metabolic pathways converge to NAD+, including tryptophan-derived de novo pathways, nicotinamide salvage pathways, nicotinic acid salvage and nucleoside salvage pathways incorporating nicotinamide riboside and nicotinic acid riboside. Key discoveries highlight a therapeutic potential for targeting NAD+ biosynthetic pathways for treatment of human diseases. A recent emergence of understanding that NAD+ homeostasis is vulnerable to aging and disease processes has stimulated testing to determine if replenishment or augmentation of cellular or tissue NAD+ can have ameliorative effects on aging or disease phenotypes. This experimental approach has provided several proofs of concept successes demonstrating that replenishment or augmentation of NAD+ concentrations can provide ameliorative or curative benefits. Thus NAD+ metabolic pathways can provide key biomarkers and parameters for assessing and modulating organism health.

KEYWORDS:

NADH; Nicotinamide adenine dinucleotide; Nicotinamide riboside; Nicotinic acid riboside; Tryptophan; Vitamin B3

PMID:
27374990
PMCID:
PMC5521000
DOI:
10.1016/j.bbapap.2016.06.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center