Vitamins and Aging: Pathways to NAD+ Synthesis

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Vitamins and Aging: Pathways to NAD+ Synthesis John M. Denu Cell Volume 129, Issue 3, Pages 453-454 (May 2007) DOI: 10.1016/j.cell.2007.04.023 Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 1 Pathways to NAD+ Synthesis NAD+ can be generated by the de novo pathway starting with the precursor tryptophan or by the salvage pathway from the precursors nicotinamide (Nam), nicotinic acid (Na), and nicotinamide riboside (NR). All of these precursors are available from the diet. Niacin often refers to two related compounds, nicotinamide (niacinamide) and nicotinic acid. The yeast gene encoding the enzyme that catalyzes each step of NAD+ biosynthesis is indicated; recently discovered portions of the salvage pathway are shown in blue. One arm of the salvage pathway requires the phosphorylation of NR to nicotinamide mononucleotide (NMN) by the NR kinase Nrk1. The other pathway involves the cleavage of the NR glycosidic bond by Pnp1 (a phosphorylase) and Urh1 (a hydrolase) to yield free nicotinamide. Whereas higher eukaryotes can readily convert nicotinamide to NMN through the action of the salvage pathway enzyme nicotinamide phosphoribosyl transferase (Revollo et al., 2007), yeast primarily hydrolyze nicotinamide to nicotinic acid through the nicotinamidase Pnc1 (Anderson et al., 2003). Curiously, mammals do not appear to have a nicotinamidase. (Bna6, quinolinate phosphoribosyl transferase; Qns1, NAD synthetase; Nma, nicotinate mononucleotide adenyltransferase; Npt, nicotinate phosphoribosyl-transferase; PRPP, phosphoribosyl pyrophosphate.) Cell 2007 129, 453-454DOI: (10.1016/j.cell.2007.04.023) Copyright © 2007 Elsevier Inc. Terms and Conditions