Figure 2. A schematic of mammalian NAD metabolism.

Metabolites are shown in plain text and enzymes in blue boxes. Abbreviations for enzymes are as follows: PARP, poly(ADP-ribose) polymerase; NAMPT, nicotinamide phosphoribosyl transferase; NMNAT, nicotinamide mononucleotide adenylyl transferase; NAPRT, nicotinic acid phosphoribosyl transferase; NADS, NAD synthase. PARP reactions require β-NAD⁺ as a substrate and generate nicotinamide as a by-product of the PARSylation of proteins. In cells where PARPs are highly active, β-NAD⁺ is largely provided by a salvage pathway that utilizes nicotinamide. Nicotinamide is processed back to β-NAD⁺ by two enzymes, NAMPT and NMNAT, with NAMPT catalysis representing the rate limiting step in this process. Alternatively, β-NAD⁺ can be synthesized de novo from either nutritional tryptophan (via the kynurenine pathway) or via NA, which is processed by NAPRT, NMNAT and NADS.