Figure 4.

Map of the NAD±biosynthetic pathway. To clarify the interpretation of the ‘in vivo' experiments described in the test, the NAD⁺ biosynthetic pathway is schematically reported: NAD⁺ can be synthesized from tryptophan (de novo synthesis) or nicotinic acid -NicA- or nicotinamide -Nam- (salvage pathway). NAD⁺ synthesis via tryptophan is performed by several reactions that lead to quinolinic acid (Quin) synthesis: this is next converted into nicotinic acid mononucleotide (NAMN) and NAMN to desamido-NAD (NAAD) and eventually into NAD⁺. Diversely, in the major salvage pathway of NAD⁺ synthesis, NAM can be converted into nicotinamide mononucleotide (NMN) by nicotinamide phosphoribosyltransferase (NAMPT) and NMN is further converted into NAD⁺ by NMN adenylyltransferase (NMNAT 1 and 2 nuclear and cytoplasmic isoforms respectively, NMNAT3 mitochodrial isoform). The asterisk indicates a reaction, catalyzed by NAD⁺ glycohydrolase, which bears close similarity with the family of ADP ribosyl cyclases. However, all the NAD⁺-transforming enzyme families mentioned above (i.e., Mono ADP-ribosyl transferases, PARP_s, sirtuins) share with ADP ribosyl cyclases/NAD⁺ glycohydrolases the property of releasing NAM from NAD⁺