Nicotinamide adenine dinucleotide biosynthetic pathway (NAD^+ biosynthetic pathway)

The **Nicotinamide adenine dinucleotide biosynthetic pathway** consists of interconnected routes for the synthesis and maintenance of NAD^+ in cells, encompassing the de novo pathway (primarily from tryptophan via the kynurenine pathway), the Preiss-Handler pathway (from nicotinic acid), and salvage pathways (mainly recycling nicotinamide, NA, NR, and NMN)[1][2][4][5]. These multi-step metabolic processes are catalyzed by numerous enzymes (notably NAMPT, NMNAT, QPRT, TDO, IDO, and others) and are crucial for sustaining cellular NAD^+ pools, which regulate energy production, redox balance, DNA repair, epigenetic control, and signaling[1][2][5]. NAD^+ metabolism is highly relevant in cancer, neurodegenerative disorders, immunity, and aging, serving both as a direct target for small molecule therapies and as a modulatory node for indirect interventions[3][5]. Therapeutic manipulation includes supplementing NAD^+ precursors, inhibiting key enzymes, and targeting pathway intermediates, with safety concerns arising from broad metabolic roles and links to tumorigenesis and immune evasion[3]. Note: The pathway itself is not a single protein, receptor, or enzyme but a metabolic network involving multiple targets; therapeutic interventions thus usually focus on individual NAD^+ biosynthetic enzymes or modulators within this pathway rather than the pathway as a whole[1][2][5].

Other names

NAD biosynthesis pathwayNAD^+ metabolismNAD synthesis pathwayKynurenine pathway (for de novo biosynthesis)Preiss-Handler pathway (for nicotinic acid salvage)NAD^+ salvage pathway

Substrate supplementation increases NAD^+ pool (NAM, NA, NMN, NR); Enzyme inhibition (NAMPT inhibitors block salvage pathway, ACMSD inhibitors modulate de novo pathway); Modulation of NAD^+ levels influences sirtuin/PARP/CD38 activities; Redox state modulation affects cell signaling and metabolic flux