NAMPT

NAMPT is the rate-limiting enzyme in this pathway and converts NAM to nicotinamide mononucleotide (NMN) by catalyzing the reversible addition of a ribose group from 5-phospho-α-D-ribosyl 1-pyrophosphate (PRPP) to NAM. To facilitate this reaction, NAMPT is autophosphorylated on H247, which enhances the affinity for NAM by 160,000-fold and increases enzymatic activity by 1,125-fold. Given that NAMPT is the rate-limiting enzyme in a key NAD recycling pathway, small changes in NAMPT activity can dramatically impact NAD metabolism and NAD dependent cellular processes. NAMPT was originally identified as a secreted cytokine-like factor that synergized with interleukin-7 and stem cell factor to promote pre-B-cell colony formation and, therefore, was initially designated PBEF (pre-B-cell enhancing factor). 
NAMPT is ubiquitously expressed in all tissues and the coding sequence is highly conserved across mammalian species and lower organisms such as insects, sponges and prokaryotes. In most cell types, NAMPT is expressed intracellularly in the cytoplasm, nucleus, and mitochondria and is commonly referred to as iNAMPT (intracellular NAMPT). A second, secreted form of NAMPT has also been observed and is referred to as eNAMPT (extracellular NAMPT) or visfatin. Enzymatic activity of eNAMPT has been demonstrated in NAMPT haplodeficient mice in which expression of eNAMPT is decreased resulting in lower plasma NMN levels and defective insulin secretion in pancreatic β –cells upon glucose stimulation. eNAMPT promoted macrophage survival following endoplasmic stressors or apoptotic inducers that are observed in obesity-associated diseases by stimulating interleukin-6 secretion and subsequent STAT3 activation.

References

1.Sampath D, et al. Pharmacol Ther. 2015;151:16–31.