Nicotinamide phosphoribosyltransferase, Nicotinamide mononucleotide adenylyltransferase (NAMPT, NMNAT)

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway, converting nicotinamide and PRPP to nicotinamide mononucleotide (NMN), a crucial step in cellular NAD+ biosynthesis. It exists as both an intracellular enzyme (iNAMPT) and an extracellular cytokine-like factor (eNAMPT/visfatin), influencing inflammation and immune cell survival. NAMPT activity modulates cell viability, stress responses, metabolism, and immune modulation, making it a key enzyme in cancer, metabolic, and inflammatory pathologies. Nicotinamide mononucleotide adenylyltransferase (NMNAT) exists in three cellular isoforms (NMNAT1, NMNAT2, NMNAT3) and catalyzes the conversion of NMN to NAD+, supporting distinct metabolic and regulatory processes according to compartmental localization. NMNATs are essential for cell survival, influence sirtuin and PARP activities, and are relevant to DNA repair, neuroprotection, and metabolic regulation. Note: These two enzymes should not be conflated; each has a unique role and therapeutic relevance but are sometimes sequentially targeted in NAD+-related therapies.

Other names

Pre-B-cell colony-enhancing factor 1 (PBEF1)Visfatin (eNAMPT)NMN pyrophosphorylaseNicotinamide mononucleotide pyrophosphorylaseNMN synthetaseNMNAT1NMNAT2NMNAT3NAD+ synthase

For inhibitors: Inhibition of NAD+ biosynthesis, leading to depletion of NAD+ and inducing apoptosis in cancer cells. For activators: Enhancement of NAD+ salvage pathway, potential neuroprotection, and metabolic benefit.