Nicotinamide phosphoribosyltransferase (NAMPT), EC 220.127.116.11, is an enzyme that catalyzes the transfer of a phosphoribosyl group to nicotinamide (NAM), forming nicotinamide mononucleotide (NMN), which is then converted to nicotinamide adenine dinucleotide (NAD). The formation of NMN is the rate limiting step for the synthesis of NAD, an important intermediate of cell metabolism and redox reactions. Next NAD-dependent enzymes, such as poly (ADP-ribose) polymerase (PARP) and sir2-like family deacetylases, catalyze NAD to produce NAM (the predominant NAD precursor in mammals), which is then recycled by NAMPT, completing the cycle.
NAMPT exists in two forms, intracellular (iNAMPT) and extracellular (eNAMPT). iNAMPT is found in the nucleus, cytoplasm and mitochondria, whereas eNAMPT is found in the extracellular space. The role of iNAMPT is clearly defined as a NAD biosynthetic enzyme. It regulates NAD levels and recycles NAM, which in turn modulates cell metabolism, oxidative stress and inflammation. However the role of eNAMPT (previously known as visfatin and pre-B-cell colony-enhancing factor 1) has not yet been fully defined; current theories include a role as a proinflammatory cytokine, insulin mimetic and NAD biosynthetic enzyme.
Overexpression of NAMPT plays a key role in cancer metabolism because of its modulatory effects on glucose and lipid metabolism, oxidative stress and inflammation. Increased levels of iNAMPT in some cancers, have been linked to angiogenesis through aberrant activation of ERK1/2 pathways, and induction of vascular endothelial growth factor (VEGF) and matrix metalloprotease (MMP) secretion. NAMPT levels are also increased in inflammatory diseases such as Crohn's disease, with eNAMPT possibly acting as a proinflammatory cytokine. Abnormal NAMPT activity has also been linked to diabetes by influencing insulin resistance.View all products for NAMPT »
Literature for NAMPT
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Genetic changes and epigenetic modifications in cancer cells alter the regulation of cellular metabolic pathways. These distinct metabolic circuits could provide viable cancer therapeutic targets. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the main targets for cancer metabolism researchers.Request copy | Download PDF | View all posters
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