NAD+ (Nicotinamide Adenine Dinucleotide)

Nicotinamide Adenine Dinucleotide (NAD+) is a critical cellular coenzyme found in all living cells, functioning in two distinct capacities: as an electron carrier in redox reactions and as a cosubstrate for NAD+-consuming enzymes. In its redox role, NAD+ and its reduced form NADH serve as the primary electron carriers in cellular metabolism: NAD+ accepts hydride ions (H-) from metabolic intermediates in glycolysis, the TCA cycle, and beta-oxidation, transferring them to the electron transport chain (Complex I) for ATP production via oxidative phosphorylation. This redox cycling is fundamental to cellular energy production. In its cosubstrate role, NAD+ is consumed by three major enzyme families: (1) Sirtuins (SIRT1-7) — NAD+-dependent protein deacetylases that remove acetyl groups from target proteins (histones, transcription factors, metabolic enzymes), linking cellular NAD+ status to gene expression, metabolic regulation, and longevity signalling. Sirtuin activity is directly dependent on NAD+ availability, making NAD+ a metabolic sensor that modulates sirtuin-mediated pathways including PGC-1alpha activation (mitochondrial biogenesis), FOXO transcription factor activation (stress resistance), and p53 deacetylation. (2) Poly(ADP-ribose) polymerases (PARPs) — NAD+-consuming enzymes involved in DNA repair signalling. (3) CD38/CD157 ectoenzymes — NAD+-degrading enzymes involved in calcium signalling.