Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans.
NAD+ is essential for life in all organisms, both as a coenzyme for oxidoreductases and as a source of ADPribosyl groups used in various reactions, including those that retard aging in experimental systems. Nicotinic acid and nicotinamide were defined as the vitamin precursors of NAD+ in Elvehjem's classic discoveries of the 1930s. The accepted view of eukaryotic NAD+ biosynthesis, that all anabolism flows through nicotinic acid mononucleotide, was challenged experimentally and revealed that nicotinamide riboside is an unanticipated NAD+ precursor in yeast. Nicotinamide riboside kinases from yeast and humans essential for this pathway were identified and found to be highly specific for phosphorylation of nicotinamide riboside and the cancer drug tiazofurin. Nicotinamide riboside was discovered as a nutrient in milk, suggesting that nicotinamide riboside is a useful compound for elevation of NAD+ levels in humans.
Bieganowski
Pawel
P
Departments of Genetics and Biochemistry and the Norris Cotton Cancer Center, Dartmouth Medical School, Rubin 733-HB7937, Lebanon, NH 03756, USA.
Brenner
Charles
C
D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D019143:Evolution, Molecular; D005658:Fungi / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009243:NAD / Q000096:biosynthesis*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D009705:Nucleosides / Q000737:chemistry; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D011726:Pyridinium Compounds; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D047908:Intracellular Signaling Peptides and Proteins; D009705:Nucleosides; D011726:Pyridinium Compounds; D029701:Saccharomyces cerevisiae Proteins; C018613:nicotinamide-beta-riboside; D009243:NAD; C076145:3-(1-deoxyribofuranosyl)benzamide; D009536:Niacinamide; D012254:Ribavirin; C403446:NMRK2 protein, human; C487432:NRK1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); C061783:nicotinamide riboside kinase; C487431:NMRK1 protein, human; C033706:tiazofurin