NAMPTs

NAMPTs, or nicotinamide phosphoribosyltransferases, are a group of enzymes that catalyze the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate (PRPP) to form nicotinamide mononucleotide (NMN). This reaction represents the first and often rate-limiting step of the NAD+ salvage pathway, supplying NMN that is subsequently converted to NAD+ by NMNAT enzymes. NAD+ is a critical cofactor in redox reactions and a substrate for enzymes such as sirtuins and PARPs.

In most cells, NAMPT functions as a cytosolic enzyme, providing NMN for intracellular NAD+ pools. A secreted form, extracellular NAMPT (eNAMPT), has been reported in adipose tissue and other cell types and has been referred to as visfatin or PBEF. The physiological role of eNAMPT is debated, with proposed functions as a cytokine or adipokine, though its extracellular enzymatic activity remains a topic of investigation.

Genetically, NAMPT is encoded by the NAMPT gene in humans and has orthologs across bacteria and eukaryotes, reflecting the evolutionary conservation of NAD+ biosynthesis. The enzyme belongs to the NAMPT family and requires divalent cations, such as Mg2+, for activity. Its activity is regulated by cellular energy status, transcriptional control, and inflammatory signals, linking NAD+ metabolism to metabolic and stress responses.

Clinical and research relevance centers on NAMPT’s role in metabolism, aging, and disease. Altered NAMPT expression or function has been associated with metabolic disorders, obesity, diabetes, cancer, and inflammatory conditions. Pharmacological NAMPT inhibitors are explored as potential cancer therapies, though challenges related to toxicity and specificity remain.