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Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2009 Jan 02; Vol. 284 (1), pp. 158-164. Date of Electronic Publication: 2008 Nov 11. - Publication Year :
- 2009
-
Abstract
- NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification.
- Subjects :
- Histone Deacetylases genetics
Histone Deacetylases metabolism
Humans
NAD genetics
Niacinamide genetics
Phosphotransferases (Alcohol Group Acceptor) genetics
Purine-Nucleoside Phosphorylase genetics
Saccharomyces cerevisiae genetics
Silent Information Regulator Proteins, Saccharomyces cerevisiae genetics
Silent Information Regulator Proteins, Saccharomyces cerevisiae metabolism
Sirtuin 2
Sirtuins genetics
Sirtuins metabolism
NAD metabolism
Niacinamide metabolism
Phosphotransferases (Alcohol Group Acceptor) metabolism
Purine-Nucleoside Phosphorylase metabolism
Saccharomyces cerevisiae metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 284
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19001417
- Full Text :
- https://doi.org/10.1074/jbc.M807976200