WHAT IS NAD+?

Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme, a form of vitamin B3 found in all organic cells that takes part in the hundreds of metabolic reactions in the body. It comprises two nucleotides connected through their phosphate groups. Each nucleotide consists of a ribose ring, where one is attached with adenosine and the other with nicotinamide at their carbon no 1. During the redox reaction, one hydrogen is transferred to the nicotinamide ring of NAD+, and the other one is transferred to carbon four of the opposite nitrogen group. The reaction of NADH and NAD+ is reversible having both reducing and oxidising properties. This property makes it a powerful reducing agent.

NAD+ is synthesised by two pathways in the living cells, the de novo and the salvage pathway. In the de novo pathway, it is synthesised from the amino acids, and in the salvage pathway, by recycling already manufactured products such as nicotinamide and NAD+. De novo synthesis involves the generation of quinolinic acid from tryptophan or aspartic acid amino acids. Then nicotinic acid mononucleotide(NaMN) is produced by the quinolinic acid by transferring a phosphate group. Adenylation of NaMN converts it into nicotinic acid adenine dinucleotide(NaAD). 

Finally, the amidation of NaAD transforms it into NAD. The salvage pathway is the key source of NAD in mammalian cells. It produces nicotinamide by recycling, utilizing NAD. The first step is the rate-limiting step in which an enzyme, Nicotinamide phosphoribosyltransferase, synthesises nicotinamide mononucleotide, a precursor of NAD. The salvage pathway of humans is different from microorganisms.

It is found in two forms, one is reduced (NADH), and the other is oxidised (NAD+) and takes part in redox reactions of the body that involve the transfer of an electron from one reaction to another reaction. But also an important cofactor in NAD+ dependent enzyme reactions. It directly involves chemical reactions and plays a role in transcriptional and translational modifications, signal transductions, and DNA repair.

NAD is an essential cosubstrate and coenzyme in biological reactions including glycolysis, tricarboxylic acid cycle, and signalling pathway due to its degrading properties. ADP- ribosylation, ribosylation, ribosylation, and PARylation are translational and protein modifications that require NAD+. It is also documented as a molecule that takes part in extracellular signalling and cell to cell communication. NAD is recognised as a transmitter released from neurons in the intestine, urinary bladder, and blood vessels. It is supposed to transmit signals from the brain to smooth muscles, acting as a neurotransmitter.

Enzymes that use NAD+ have a significant role in disease management and pharmacology. It is found in abundance in the cytoplasm, nucleus, and mitochondria.

Drugs target it in three ways:

  1. Prevent NAD+ synthesis,
  2. Enzyme activator,
  3. Enzyme inhibitors.

It is used as a therapy for Alzheimer's, Parkinson's disease. Metabolic disorders, and cancer.

According to facts, NAD has a role in reversing the aging process, addiction recovery, weight management, energy production, athletics booster, and pain reduction. Recent research shows that the level of NAD declines with advancing age in different types of tissues such as adipose, heart, liver, spleen, kidney, lungs, spleen, and extracellular fluids. Thus NAD supplementation is beneficial in the aging process.


Conclusion

NAD+ is a coenzyme that is found in cells and takes part in cellular respiration. It is synthesised in the cells by the salvage pathway and de novo pathway.  The NAD+ and NADH act as both reducing and oxidising agents that are important in different chemical reactions in the cell.


References

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  3. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x. Epub 2020 Dec 22. PMID: 33353981; PMCID: PMC7963035.
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