Title | NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Yang Y, Sauve AA |
Journal | Biochim Biophys Acta |
Volume | 1864 |
Issue | 12 |
Pagination | 1787-1800 |
Date Published | 2016 Dec |
ISSN | 0006-3002 |
Keywords | Animals, Energy Metabolism, Humans, Metabolic Diseases, Metabolic Networks and Pathways, Models, Biological, NAD, NADP, Niacin, Niacinamide, Nucleosides, Signal Transduction, Sirtuins, Tryptophan |
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. |
DOI | 10.1016/j.bbapap.2016.06.014 |
Alternate Journal | Biochim Biophys Acta |
PubMed ID | 27374990 |
PubMed Central ID | PMC5521000 |
Grant List | P30 DK026687 / DK / NIDDK NIH HHS / United States R01 GM106072 / GM / NIGMS NIH HHS / United States R21 DK094001 / DK / NIDDK NIH HHS / United States |