De novo synthesis begins with tryptophan, which is converted to NaMN in six enzymatic steps. NaMN is then adenylylated by Nma1 and Nma2 to NaAD, which is converted to NAD+ by glutamine-dependent NAD+ synthetase, Qns1. NaMN is also formed by salvage of Nam, via nicotinamidase, Pnc1, and nicotinic acid phosphoribosyltransferase, Npt1. Environmental NA also generates NaMN via the phosphoribosylation activity of Npt1. NR is converted to NMN via Nrk1, then to NAD+ by Nma1 and Nma2. Additionally, NAR can utilize Nrk1-dependent phosphorylation and both NR and NAR can be converted to NAD+ in Nrk1-independent pathways initiated by nucleoside splitting activities. The nucleosides NR and NAR are produced intracellularly by the 5'-nucleotidase activities of Sdt1 and Isn1 acting on NMN and NAR. NAD+ is broken down by the sirtuins, Sir2 and Hst1-4.
Evans et al. BMC Chemical Biology 2010 10:2 doi:10.1186/1472-6769-10-2