Description

NAD+ (Nicotinamide Adenine Dinucleotide) is a naturally occurring nucleotide that plays a central role in cellular metabolism, energy production, and DNA repair. It is also believed to function as a secondary messenger, participating in calcium-dependent signaling pathways and potentially contributing to immune regulation.

NAD+ is synthesized naturally via the de novo pathway, converting the amino acid tryptophan through several enzymatic steps. It can also be formed from precursors such as nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinamide mononucleotide. Once synthesized, NAD+ participates in over 500 enzymatic reactions, serving as a coenzyme in redox reactions and being converted to NADH, the energy-carrying form critical for metabolic processes.

Overview

NAD+ interacts with three major classes of enzymes, often referred to as NAD+-dependent enzymes:

• Sirtuins (SIRTs): Deacetylase enzymes involved in mitochondrial function, stem cell regeneration, and neuroprotection, supporting cellular homeostasis.

• Poly ADP Ribose Polymerases (PARPs): A family of 17 enzymes that use NAD+ to synthesize poly ADP ribose polymers, contributing to genome stability and DNA repair.

• Cyclic ADP Ribose Synthetases (cADPRS): Enzymes such as CD38 and CD157, which hydrolyze NAD+ and are linked to stem cell regeneration, DNA repair, and immune function.

Because all three enzyme classes depend on NAD+, they may compete for NAD+ availability, highlighting the importance of maintaining optimal NAD+ levels for balanced cellular function. Proper NAD+ balance may maximize metabolic efficiency, genomic stability, and cellular repair mechanisms.

Reference

https://pubmed.ncbi.nlm.nih.gov/?term=NAD

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