Nicotinamide adenine dinucleotide metabolism pathway (NAD+ metabolism)

The Nicotinamide adenine dinucleotide (NAD+) metabolism pathway is a fundamental biochemical network that maintains the balance of NAD+, a coenzyme essential for cellular energy production and signaling. NAD+ acts as a critical electron carrier in redox reactions, such as glycolysis and the citric acid cycle, and serves as a necessary substrate for enzymes including sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38 (Canto et al., 2015, Cell Metabolism). These enzymes regulate vital processes such as DNA repair, genomic stability, and epigenetic modifications. Because NAD+ levels decline with age and in various disease states, the pathway is a primary focus for therapeutic intervention in neurodegeneration, metabolic syndrome, and cardiovascular diseases (Yoshino et al., 2018, Cell Metabolism). Strategies to modulate this pathway include the administration of NAD+ precursors like nicotinamide riboside (NR) to boost levels, or the use of inhibitors against NAD+-consuming enzymes to preserve the pool. In contrast, in oncology, the pathway is targeted for inhibition, specifically through NAMPT inhibitors, to deplete NAD+ and starve cancer cells of the energy required for rapid proliferation (Gallí et al., 2013, Cancer Research).

Other names

NAD+ biosynthesisNAD+ salvage pathwayNAD+ cyclePyridine nucleotide metabolism

Therapeutic intervention involves boosting NAD+ levels via precursors (NR, NMN), inhibiting NAD+ consuming enzymes (CD38, PARPs) to preserve levels, or inhibiting rate-limiting biosynthetic enzymes (NAMPT) to deplete NAD+ in cancer cells.