FIGURE 8.

Revised model of NAD⁺ metabolism in yeast. New steps in NAD⁺ metabolism, consisting of the NMN/NaMN 5′-nucleotidase activities of Isn1 and Sdt1, are depicted in red. New regulatory steps, also depicted in red, show that Isn1 protein accumulation is promoted by NA and opposed by CR. These data suggest a novel mechanism by which CR can control NAD⁺ metabolism and availability for Sir2-dependent reactions: by retarding NAD⁺ catabolic pathways mediated by Isn1, CR may direct NAD⁺ flux toward Sir2 utilization.