Abstract |
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NAD is best known as electron carrier and co-substrate of various redox reactions. However, over the past 20 years, NAD has been shown to be a key signaling molecule that mediates post-translational protein modifications and serves as precursor of ADP-ribose containing messenger molecules, which are involved in calcium mobilization. In contrast to its role as redox-carrier NAD-dependent signaling processes involve the release of nicotinamide (Nam) and require a constant replenishment of cellular NAD pools. So far, very little is known about the evolution of NAD(P) synthesis in eukaryotes. In the present study, genes of the NAD(P) metabolism in 45 species were identified and analyzed regarding similarities and differences in NAD(P) synthesis. The results strikingly show that the Preiss-Handler pathway and NAD kinase are present in all organisms investigated and thus seem to be ancestral routes. Additionally, two pathways exist that convert Nam to NAD, which so far have been thought to exclude each other. However, we identified several species that bear apparently functional copies of both biosynthetic routes. Furthermore, our findings suggest a parallel phylogenetic appearance of nicotinamide N-methyltransferase (NNMT), Nam phosphoribosyl transferase (NamPRT) and poly-ADP-ribosyltransferases (PARPs).