NAD+

Also known as: Nicotinamide Adenine Dinucleotide, β-NAD+

NAD+ (nicotinamide adenine dinucleotide) is an essential coenzyme in cellular energy metabolism, sirtuin activation, and DNA repair. Research documents its role in mitochondrial function, aging biology, and neuroprotection.

NAD+
For Research Use Only

Molecular Formula

C₂₁H₂₇N₇O₁₄P₂

Molecular Weight

663.4 Da

Key Enzymes

Sirtuins (SIRT1-7), PARPs, CD38

Redox Pair

NAD+/NADH

Ubiquity

Present in all living cells

Research Use Only

Not for human or veterinary use

Overview

Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme found in all living cells, where it participates as an electron carrier in oxidative phosphorylation and as a substrate for a diverse class of enzymes that regulate metabolism, stress responses, and aging. NAD+ levels decline with age, caloric excess, and various disease states — a decline that has become a major focus of aging biology research over the past decade.

NAD+ serves two distinct biochemical roles. As a redox carrier, NAD+/NADH couples substrate oxidation to the electron transport chain, driving ATP synthesis in mitochondria. As an enzyme substrate (rather than a cofactor), NAD+ is consumed and regenerated in reactions catalyzed by sirtuins (SIRT1-7), PARP enzymes (involved in DNA repair), and CD38 (an NADase involved in calcium signaling). This dual role means that NAD+ depletion impacts both energy production and regulatory signaling simultaneously.

Research on NAD+ supplementation strategies has grown substantially following seminal work by Guarente, Sinclair, and others demonstrating that restoring NAD+ levels in aged animals could reverse multiple age-associated phenotypes. Studies using NAD+ precursors (NMN, NR) or direct NAD+ have documented effects on mitochondrial function, sirtuin activity, PARP-mediated DNA repair, and inflammatory signaling in both cellular and animal models. NAD+ also plays a central role in the biology of circadian rhythms through NAMPT-mediated synthesis regulation.

NAD+ for research is used in cell-free biochemical assays, enzyme activity measurements, and cellular supplementation studies. Investigators working on sirtuins, PARP biology, mitochondrial metabolism, or aging mechanisms will find NAD+ an essential research reagent. Available for laboratory use only.

Mechanism of Action

In redox metabolism, NAD+ accepts hydride from metabolic substrates (glycolysis, TCA cycle, β-oxidation) to become NADH, which donates electrons to Complex I of the mitochondrial ETC. This electron flow drives the proton gradient used by ATP synthase. As a sirtuin substrate, NAD+ is cleaved during deacetylation reactions, yielding nicotinamide and O-acetyl-ADP-ribose alongside the deacetylated protein target. Sirtuin targets include histones, p53, FOXO transcription factors, and PGC-1α — making NAD+ availability a direct regulator of epigenetic and transcriptional programs.

PARP enzymes (primarily PARP1/2) consume NAD+ to synthesize poly-ADP-ribose (PAR) chains on proteins at DNA damage sites, facilitating repair. Excessive PARP activation during DNA damage can rapidly deplete cellular NAD+ stores, creating a feedforward cycle of mitochondrial dysfunction and cell death. Research with NAD+ supplementation has shown that maintaining NAD+ availability preserves SIRT1 activity and mitochondrial function even under conditions of moderate DNA damage stress.

Research Applications

Research Use Only. NAD+ is available for laboratory and research applications only. It is not approved by the FDA or any equivalent regulatory authority for human or veterinary therapeutic use. All information on this page is derived from published preclinical literature and is presented for informational and research context purposes only. Investigators should consult current primary literature and comply with applicable regulations before initiating research.

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Peptide Family

Mitochondrial Peptides & Metabolic Compounds

Bioenergetics · AMPK · Sirtuin Activation · Cardiolipin

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