NAD+ in aging, metabolism, and neurodegeneration


Salvage pathway is the key pathway for maintaining cellular NAD+ levels. The NAD+-consuming enzymesthe SIRTs, ARTs, and PARPsall generate nicotinamide as a by-product of their enzymatic activities. Nicotinamide regulates their activities as an inhibitory factor by binding in a conserved NAD+ pocket and also as a biosynthetic precursor to NAD+ via activity of nicotinamide phosphoribosyltransferase (NAMPT). This enzyme recycles nicotinamide into nicotinamide mononucleotide (NMN), which is converted into NAD+ by the various NMNATs (discussed above). This pathway leads to recycling of nicotinamide into NAD+ and relieves nicotinamide inhibition of NAD+-consuming enzymes. NAMPT is expressed in low amounts in pancreatic b cells and neurons, which might allow it to become more rapidly limiting in these cells.