NAD+ biosynthetic pathways in various organisms. (a) The de novo pathway from tryptophan and the salvage pathway through nicotinamide (NIC) and nicotinic acid (NA) in the budding yeast Saccharomyces cerevisiae. These pathways are also conserved in invertebrates. Pnc1, nicotinamidase; Npt1, nicotinic acid phosphoribosyltransferase; Nma1, 2, nicotinic acid mononucleotide adenylyltransferase 1, 2; Qns1, NAD synthetase; Qpt1, quinolinic acid phosphoribosyltransfease; Nrk1, nicotinamide ribose kinase 1; Pho5, 8, phosphatase 5, 8; Urh1, Pnp1, nucleosidases; Nnt1, nicotinamide-N-methyltransferase. (b) NAD+ biosynthetic pathways in mammals. In mammals, NAD+ can be synthesized from tryptophan, nicotinic acid (NA) and nicotinamide (NIC) (two forms of vitamin B3), and nicotinamide riboside (NR). NIC is a predominant NAD+ precursor in mammals. The de novo pathway and the NAD+ biosynthetic pathway from nicotinic acid are evolutionarily conserved, whereas the NAD+ biosynthetic pathway from nicotinamide is mediated by nicotinamide phosphoribosyltransferase (Nampt). While multiple enzymes break NAD+ into nicotinamide and ADP-ribose, only sirtuins are shown in this figure. The resultant NIC is also converted to 1-methylnicotinamide by nicotinamide-N-methyltransferase (Nnmt). Mammals have two NR kinases (Nrk1 and 2) and ecto-5′-nucleotidase CD73 to produce NMN and NR, respectively. NaMN, nicotinic acid mononucleotide; NMN, nicotinamide mononucleotide.