NAD

What’s Nicotinamide Adenine Dinucleotide NAD？

The efficacy of NAD

The effects on energy metabolism

Key role in REDOX reactions: NAD (nicotinamide adenine dinucleotide) plays a key role in metabolic pathways such as glycolysis and the tricarboxylic acid cycle within cells. In the process of glycolysis, glyceraldehyde-3-phosphate dehydrogenase catalyzes the oxidation of glyceraldehyde-3-phosphate to 1, 3-diphosphoglyceric acid, while NAD + receives electrons and protons which are reduced to NADH. For example, in the energy production process of human cells, each molecule of glucose goes through glycolysis to produce 2 molecules of NADH.
An important link in ATP production: NADH carries electrons into the electron transport chain of mitochondria. Electrons are transferred sequentially in the electron transport chain, and the released energy is used to pump protons from the mitochondrial matrix to the membrane gap, forming a proton electrochemical gradient. When protons return to the matrix via ATP synthase, they drive ATP synthesis. It is estimated that about 2.5-3 ATP molecules can be produced per pair of electrons passed through the NADH respiratory chain. This process acts like an energy conversion factory, with NADH being the “energy carrier” that efficiently converts chemical energy produced during metabolism into a form of ATP that cells can use directly.

Efficacy in cell signaling and gene expression

Regulation of metabolism-related gene expression: NAD + is involved in regulating the activity of a number of key transcription factors in cells. For example, it regulates the activity of SIRT1, a deacetylase dependent on NAD +. SIRT1 affects gene expression by deacetylating histones and some transcription factors (such as PPAR-γ). This regulatory effect can alter the metabolic program of cells, such as increasing the expression of genes related to fatty acid oxidation, and promoting the cell to use fat for energy.
Involvement in cellular stress response: When cells are exposed to stress such as oxidative stress, nutritional deficiency, there is a change in the level of NAD +, which in turn protects the cell by activating a series of stress response pathways. In the case of oxidative stress, where reactive oxygen species (ROS) produced by NADPH oxidase cause an altered intracellular REDOX state, NAD + works as a signaling molecule that regulates the expression and activity of antioxidant enzymes (e.g., superoxide dismutase, glutathione peroxidase, etc.), helping cells to clear ROS and maintaining intracellular REDOX balance.

In NAD repair

Involved in repair as a substrate for PARP: In the process of DNA damage repair, poly (ADP-ribose) polymerase (PARP) plays an important role, and NAD + is a substrate for PARP. When there is damage to DNA such as a single strand break, PARP is activated, taking advantage of NAD + synthetic poly (ADP-ribose) (PAR). Pars can be used as signaling molecules to recruit DNA repair proteins (such as XRCC1) to the damage site and promote the repair of DNA single strand breaks. If the level of NAD is insufficient, the activity of PARP is affected, leading to a decline in DNA repair capacity and increased instability in the cell’s genome.
Maintenance of genomic stability: By participating in DNA repair, NAD + contributes to the maintenance of genomic integrity. At all stages of the cell cycle, especially during the S phase (DNA synthesis phase) and G2 phase (late DNA synthesis phase), NAD + is essential for the timely repair of damage produced during DNA replication. This prevents the accumulation of DNA damage and reduces the risk of cells becoming mutated and cancerous.