Discussion
A revised metabolic scheme for NAD+, incorporating Nrk1 homologs and the nicotinamide riboside salvage pathway is shown in Figure 6. A little appreciated difference between humans and yeasts concerns the organisms' uses of nicotinamide and nicotinic acid, the compounds coidentified as anti black tongue factor (Elvehjem et al., 1938). Humans encode a homolog of the Haemophilus ducreyi nadV gene, termed pre-B-cell colony enhancing factor, that may convert nicotinamide to NMN (Rongvaux et al., 2002), which is highly induced during lymphocyte activation (Samal et al., 1994). In contrast, S. cerevisiae lacks a homolog of nadV and instead has a homolog of the E. coli pncA gene, termed PNC1, that converts nicotinamide to nicotinic acid for entry into the Preiss-Handler pathway (Ghislain et al. 2002, Sandmeier et al. 2002). Though the Preiss-Handler pathway is frequently considered a salvage pathway from nicotinamide, it technically refers to the steps from nicotinic acid to NAD+ (Preiss and Handler 1958a, Preiss and Handler 1958b). Reports that nicotinamidase had been purified from mammalian liver in the 1960s (Petrack et al., 1965) may have contributed to the sense that fungal and animal NAD+ biosynthesis is entirely conserved. However, animal genes for nicotinamidase have not been identified and there is no compelling evidence that nicotinamide and nicotinic acid are utilized as NAD+ precursors through the same route in mammals. The persistence of “niacin” as a mixture of nicotinamide and nicotinic acid may attest to the utility of utilizing multiple pathways to generate NAD+ and suggests that supplementation with nicotinamide riboside as third importable NAD+ precursor may be beneficial for certain conditions.