title: NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.
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.
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: aas2004@med.cornell.edu.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Sauve
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000378:metabolism / Q000628:therapy; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009525:Niacin / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
chemical_list: D009705:Nucleosides; D009243:NAD; D009536:Niacinamide; D009525:Niacin; D009249:NADP; D014364:Tryptophan; D037761:Sirtuins
keywords: NADH; Nicotinamide adenine dinucleotide; Nicotinamide riboside; Nicotinic acid riboside; Tryptophan; Vitamin B3