Nicotinamide adenine dinucleotide metabolic pathway (NAD+ metabolic pathway) (NAD+ metabolic pathway)

The Nicotinamide adenine dinucleotide (NAD+) metabolic pathway is a complex network of biochemical reactions responsible for the synthesis, conversion, and degradation of NAD+ and its related nucleotides (Source: PubMed, PMID: 29414321). NAD+ is a fundamental coenzyme that facilitates redox reactions in essential metabolic processes like glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (Source: NIH/NCBI). In addition to its role in energy production, NAD+ acts as a necessary substrate for several families of enzymes, including sirtuins, poly(ADP-ribose) polymerases (PARPs), and cyclic ADP-ribose synthases like CD38 (Source: Nature Reviews Molecular Cell Biology). These enzymes regulate critical cellular functions such as DNA repair, genomic stability, circadian rhythms, and calcium-mediated signaling. Depletion of NAD+ levels is a hallmark of aging and is associated with various age-related diseases, including neurodegeneration and metabolic disorders (Source: Wikipedia). Conversely, many cancer cells upregulate NAD+ biosynthetic enzymes, such as nicotinamide phosphoribosyltransferase (NAMPT), to support their high metabolic demands and survival (Source: PubChem). Therapeutic interventions targeting this pathway involve either replenishing NAD+ pools using precursors like nicotinamide riboside (NR) or inhibiting specific enzymes to treat cancer or inflammatory conditions. Because NAD+ is ubiquitous and involved in numerous physiological processes, pharmacological modulation of this pathway requires precise targeting to balance therapeutic efficacy with potential systemic side effects.

Other names

NAD+ metabolismNAD+ biosynthetic pathwayNAD+ salvage pathwayPreiss-Handler pathwayDe novo NAD+ synthesis pathway

Modulation of cellular NAD+ levels through the administration of biosynthetic precursors (e.g., NR, NMN), the inhibition of rate-limiting biosynthetic enzymes (e.g., NAMPT inhibitors), or the inhibition of NAD+-consuming enzymes (e.g., PARP or CD38 inhibitors).