nicotinamideadeninedinucleotide

Nicotinamide adenine dinucleotide (NAD) is a dinucleotide coenzyme found in all living cells. It consists of two nucleotides linked by a phosphodiester bond: one containing the adenine base and the other containing the nicotinamide moiety. NAD exists in oxidized (NAD+) and reduced (NADH) forms and plays a central role in cellular energy metabolism.

As an electron carrier, NAD+ accepts a hydride from fuel molecules to become NADH, which can donate electrons to the mitochondrial electron transport chain to drive ATP synthesis. The NAD+/NADH ratio influences many metabolic pathways, and shifts in this ratio reflect the cell’s redox state and energy status. In addition to redox chemistry, NAD+ serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38, linking metabolism to signaling, DNA repair, and calcium signaling.

Biosynthesis and precursors: NAD+ can be produced de novo from tryptophan or generated via salvage pathways that recycle nicotinamide and nicotinic acid. A key step in salvage involves NAMPT converting nicotinamide to nicotinamide mononucleotide (NMN), which is then converted to NAD+ by NMNAT enzymes. Nicotinamide riboside is another precursor that feeds into this pathway.

Related coenzyme: NADP+/NADPH is a phosphorylated counterpart used primarily in reductive biosynthesis and antioxidant defense.

Physiology and clinical relevance: NAD+ levels decline with aging and in some metabolic disorders. Supplements such as nicotinamide riboside or NMN are being investigated for potential benefits on mitochondrial function and metabolic health, though clinical evidence remains under study. NAD+ is essential for energy production and a wide array of cellular processes, making it a central focus of metabolic and aging research.