NAD+ biosynthetic pathway

The term "NAD+ biosynthetic pathway" refers not to a single molecule or a receptor, but rather to a network of enzymatic reactions responsible for the cellular synthesis and recycling of NAD+ (nicotinamide adenine dinucleotide), a crucial metabolic coenzyme involved in redox reactions, energy metabolism, DNA repair, and cell signaling[3][5][7]. Multiple precursor molecules (tryptophan, nicotinamide, nicotinic acid, nicotinamide riboside, nicotinamide mononucleotide) and several key enzymes (e.g., NAMPT, NAPRT, NMNAT) participate in this pathway, using either de novo synthesis from tryptophan or salvage routes from vitamin B3 metabolites[3][5][7]. Dysregulation of NAD+ biosynthetic enzymes is implicated in cancer, aging, neurodegeneration, and metabolic diseases, and expression levels of enzymes such as NAMPT and NAPRT can affect prognosis and therapeutic response in cancer[1][2][3]. However, as a pathway, "NAD+ biosynthetic pathway" is not a druggable molecular target in the sense of a single protein, receptor, or enzyme, though individual constituent enzymes (especially NAMPT or NAPRT) are established therapeutic targets[2][4]. Therefore, for structured therapeutic target information, specific enzymes within this pathway should be considered, not the pathway as a whole.

Inhibition of NAD+ biosynthetic enzymes (e.g., NAMPT, NAPRT), Supplying NAD+ precursors to increase NAD+ levels, Inhibiting NAD+-consuming enzymes (e.g., PARP, CD38), Allosteric activation of sirtuins