Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans

  title={Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans},
  author={Paweł Bieganowski and Charles Brenner},

Figures and Tables from this paper

Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production
It is shown that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites, and the data indicate that NAD+ metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD+, metabolism by balancing import and export of NAD+ precursor vitamins.
Saccharomyces cerevisiae YOR071C Encodes the High Affinity Nicotinamide Riboside Transporter Nrt1*
Deletion of a single gene, YOR071C, fully restores nicotinamide riboside import and utilization when resupplied to mutant yeast cells and extends replicative life span on high glucose medium.
Coupling of NAD+ Biosynthesis and Nicotinamide Ribosyl Transport: Characterization of NadR Ribonucleotide Kinase Mutants of Haemophilus influenzae
The data demonstrate that the NR phosphorylation step is essential for both NR uptake across the inner membrane and NAD+ synthesis and is also involved in controlling the NAD+ biosynthesis rate.
Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD+
Crystal structures of Nrk1 led to the identification of new pathways to NAD+, and an enzyme structurally similar to Rossmann fold metabolite kinases was identified to recognize the distinctive carboxamide group of nicotinamide riboside.
Identification of Isn1 and Sdt1 as Glucose- and Vitamin-regulated Nicotinamide Mononucleotide and Nicotinic Acid Mononucleotide 5′-Nucleotidases Responsible for Production of Nicotinamide Riboside and Nicotinic Acid Riboside*
It is shown that nicotinamide riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast and reveal unanticipated and highly regulated steps in NAD+ metabolism.
Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis.
It is shown that Arabidopsis thaliana gene At2g22570 encodes a nicotinamidase, which is expressed in all tissues, with the highest levels observed in roots and stems, and that the growth of the roots of wild-type but not nic1-1 mutant plants is inhibited and distorted by nicotinamide.
Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals
It is demonstrated that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside Hydrolase than as a uridineHydrolase and that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphoryLase is responsible for mammalian nicotinic acid Riboside kinase-independent nicotinism ribosid utilization.
The Leishmania nicotinamidase is essential for NAD+ production and parasite proliferation
The results illustrate that NAD+ homeostasis is a fundamental component of Leishmania biology and virulence, and that NAm constitutes its main NAD+ source in the mammalian host.
Synthesizing and Salvaging NAD+: Lessons Learned from Chlamydomonas reinhardtii
A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells and is suggested to be an excellent model system to study NAD+ metabolism and cell longevity.


Ribosylnicotinamide Kinase Domain of NadR Protein: Identification and Implications in NAD Biosynthesis
A model for the complete salvage pathway from exogenous N-ribosylnicotinamide to NAD which involves the concerted action of the PnuC transporter and NRK, followed by the NMNAT activity of the NadR protein is proposed.
Enzymology of NAD+ homeostasis in man
The regulation of NAD+ homeostasis with respect to the physiological role played by the enzymes both utilizing NAD+ through the nonredox NAD+-dependent reactions and catalyzing the recycling of the common product, nicotinamide, is discussed.
Eukaryotic NAD+ Synthetase Qns1 Contains an Essential, Obligate Intramolecular Thiol Glutamine Amidotransferase Domain Related to Nitrilase*
Data indicate that the nitrilase-related domain in Qns1 is the fourth independently evolved glutamine amidotransferase domain to have been identified in nature and that glutamine-dependence is an obligate phenomenon involving intramolecular transfer of ammonia over a predicted distance of 46 Å from one active site to another withinQns1 monomers.
New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism
The ability to isolate mutants resistant to 5-fluorocytidine which mapped to five other loci demonstrated the existence of a complex cytidine metabolic network.
Role of adenosine kinase in Saccharomyces cerevisiae: identification of the ADO1 gene and study of the mutant phenotypes
It is proposed that the physiological role of adenosine kinase in S. cerevisiae could primarily be to recycleAdenosine produced by the methyl cycle.
Identification and functional analysis of the Saccharomyces cerevisiae nicotinamidase gene, PNC1
It is suggested that NAMase helps yeast cells to adapt to various stress conditions and nutrient depletion, most likely via the activation of NAD‐dependent biological processes.
Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae
A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.
The yeast Sir2 protein, required for transcriptional silencing, has an NAD(+)-dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD(+)-dependent HDA activity that is eliminated
New functions of a long-known molecule. Emerging roles of NAD in cellular signaling.
  • M. Ziegler
  • Biology, Chemistry
    European journal of biochemistry
  • 2000
The first group of reactions leads to the synthesis of an unusual cyclic nucleotide, cyclic ADP-ribose (cADPR), which has been reported to be potent intracellular calcium-mobilizing agents and in concert with inositol 1,4,5-trisphosphate, they participate in cytosolic calcium regulation by releasing calcium from intrace cellular stores.
Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1*
It is shown here that nicotinamide strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of asir2 mutant, demonstrating that silent heterochromatin requires continual Sir2 activity.