The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Charles Brenner - One of the best experts on this subject based on the ideXlab platform.
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Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production
PloS one, 2011Co-Authors: Peter Belenky, Katrina L. Bogan, Charles R. Evans, Rebecca C. Stebbins, Charles BrennerAbstract:NAD(+) is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+) consuming enzymes. NAD(+) biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+) is synthesized from tryptophan and the three vitamin precursors of NAD(+): nicotinic acid, nicotinamide and nicotinamide Riboside. Supplementation of yeast cells with NAD(+) precursors increases intracellular NAD(+) levels and extends replicative lifespan. Here we show that both nicotinamide Riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide Riboside transporter, Nrt1, leads to increased export of nicotinamide Riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide Riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide Riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. 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.
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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
Journal of Biological Chemistry, 2009Co-Authors: Katrina L. Bogan, Peter Belenky, Charles R. Evans, Peng Song, Charles F. Burant, Robert T. Kennedy, Charles BrennerAbstract:Recently, we discovered that nicotinamide Riboside and nicotinic acid Riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide Riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide Riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide Riboside was detected with a biological assay, and intracellular levels of nicotinamide Riboside, nicotinic acid Riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide Riboside and nicotinic acid Riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.
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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
The Journal of biological chemistry, 2009Co-Authors: Katrina L. Bogan, Peter Belenky, Charles R. Evans, Peng Song, Charles F. Burant, Robert T. Kennedy, Charles BrennerAbstract:Recently, we discovered that nicotinamide Riboside and nicotinic acid Riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide Riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide Riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide Riboside was detected with a biological assay, and intracellular levels of nicotinamide Riboside, nicotinic acid Riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide Riboside and nicotinic acid Riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.
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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.
The Journal of biological chemistry, 2008Co-Authors: Peter Belenky, Kathryn C. Christensen, Francesca S. Gazzaniga, Alexandre A. Pletnev, Charles BrennerAbstract: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.
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Saccharomyces cerevisiae YOR071C Encodes the High Affinity Nicotinamide Riboside Transporter Nrt1
Journal of Biological Chemistry, 2008Co-Authors: Peter Belenky, Tiberiu G. Moga, Charles BrennerAbstract:Abstract NAD+ is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD+-consuming enzymes. Nicotinamide Riboside is a recently discovered eukaryotic NAD+ precursor converted to NAD+ via the nicotinamide Riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide Riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide Riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide Riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide Riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a Km for nicotinamide Riboside of 22 μm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide Riboside uptake.
Peter Belenky - One of the best experts on this subject based on the ideXlab platform.
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Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production
PloS one, 2011Co-Authors: Peter Belenky, Katrina L. Bogan, Charles R. Evans, Rebecca C. Stebbins, Charles BrennerAbstract:NAD(+) is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+) consuming enzymes. NAD(+) biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+) is synthesized from tryptophan and the three vitamin precursors of NAD(+): nicotinic acid, nicotinamide and nicotinamide Riboside. Supplementation of yeast cells with NAD(+) precursors increases intracellular NAD(+) levels and extends replicative lifespan. Here we show that both nicotinamide Riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide Riboside transporter, Nrt1, leads to increased export of nicotinamide Riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide Riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide Riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. 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.
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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
Journal of Biological Chemistry, 2009Co-Authors: Katrina L. Bogan, Peter Belenky, Charles R. Evans, Peng Song, Charles F. Burant, Robert T. Kennedy, Charles BrennerAbstract:Recently, we discovered that nicotinamide Riboside and nicotinic acid Riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide Riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide Riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide Riboside was detected with a biological assay, and intracellular levels of nicotinamide Riboside, nicotinic acid Riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide Riboside and nicotinic acid Riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.
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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
The Journal of biological chemistry, 2009Co-Authors: Katrina L. Bogan, Peter Belenky, Charles R. Evans, Peng Song, Charles F. Burant, Robert T. Kennedy, Charles BrennerAbstract:Recently, we discovered that nicotinamide Riboside and nicotinic acid Riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide Riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide Riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide Riboside was detected with a biological assay, and intracellular levels of nicotinamide Riboside, nicotinic acid Riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide Riboside and nicotinic acid Riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.
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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.
The Journal of biological chemistry, 2008Co-Authors: Peter Belenky, Kathryn C. Christensen, Francesca S. Gazzaniga, Alexandre A. Pletnev, Charles BrennerAbstract: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.
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Saccharomyces cerevisiae YOR071C Encodes the High Affinity Nicotinamide Riboside Transporter Nrt1
Journal of Biological Chemistry, 2008Co-Authors: Peter Belenky, Tiberiu G. Moga, Charles BrennerAbstract:Abstract NAD+ is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD+-consuming enzymes. Nicotinamide Riboside is a recently discovered eukaryotic NAD+ precursor converted to NAD+ via the nicotinamide Riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide Riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide Riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide Riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide Riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a Km for nicotinamide Riboside of 22 μm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide Riboside uptake.
Katrina L. Bogan - One of the best experts on this subject based on the ideXlab platform.
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Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production
PloS one, 2011Co-Authors: Peter Belenky, Katrina L. Bogan, Charles R. Evans, Rebecca C. Stebbins, Charles BrennerAbstract:NAD(+) is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+) consuming enzymes. NAD(+) biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+) is synthesized from tryptophan and the three vitamin precursors of NAD(+): nicotinic acid, nicotinamide and nicotinamide Riboside. Supplementation of yeast cells with NAD(+) precursors increases intracellular NAD(+) levels and extends replicative lifespan. Here we show that both nicotinamide Riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide Riboside transporter, Nrt1, leads to increased export of nicotinamide Riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide Riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide Riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. 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.
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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
Journal of Biological Chemistry, 2009Co-Authors: Katrina L. Bogan, Peter Belenky, Charles R. Evans, Peng Song, Charles F. Burant, Robert T. Kennedy, Charles BrennerAbstract:Recently, we discovered that nicotinamide Riboside and nicotinic acid Riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide Riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide Riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide Riboside was detected with a biological assay, and intracellular levels of nicotinamide Riboside, nicotinic acid Riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide Riboside and nicotinic acid Riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.
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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
The Journal of biological chemistry, 2009Co-Authors: Katrina L. Bogan, Peter Belenky, Charles R. Evans, Peng Song, Charles F. Burant, Robert T. Kennedy, Charles BrennerAbstract:Recently, we discovered that nicotinamide Riboside and nicotinic acid Riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide Riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide Riboside and nicotinic acid Riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide Riboside was detected with a biological assay, and intracellular levels of nicotinamide Riboside, nicotinic acid Riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide Riboside and nicotinic acid Riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.
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Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD
PLoS biology, 2007Co-Authors: Wolfram Tempel, Peter Belenky, Wael M. Rabeh, Katrina L. Bogan, Marzena Wojcik, Heather F. Seidle, Lyudmila Nedyalkova, Tianle Yang, Anthony A. Sauve, Hee-won ParkAbstract:The eukaryotic nicotinamide Riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide Riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide Riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide Riboside. Indeed, nicotinic acid Riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid Riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.
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Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+
Cell, 2007Co-Authors: Peter Belenky, Katrina L. Bogan, Frances G. Racette, Julie M. Mcclure, Jeffrey S. Smith, Charles BrennerAbstract:Although NAD(+) biosynthesis is required for Sir2 functions and replicative lifespan in yeast, alterations in NAD(+) precursors have been reported to accelerate aging but not to extend lifespan. In eukaryotes, nicotinamide Riboside is a newly discovered NAD(+) precursor that is converted to nicotinamide mononucleotide by specific nicotinamide Riboside kinases, Nrk1 and Nrk2. In this study, we discovered that exogenous nicotinamide Riboside promotes Sir2-dependent repression of recombination, improves gene silencing, and extends lifespan without calorie restriction. The mechanism of action of nicotinamide Riboside is totally dependent on increased net NAD(+) synthesis through two pathways, the Nrk1 pathway and the Urh1/Pnp1/Meu1 pathway, which is Nrk1 independent. Additionally, the two nicotinamide Riboside salvage pathways contribute to NAD(+) metabolism in the absence of nicotinamide-Riboside supplementation. Thus, like calorie restriction in the mouse, nicotinamide Riboside elevates NAD(+) and increases Sir2 function.
Anthony A. Sauve - One of the best experts on this subject based on the ideXlab platform.
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nicotinamide Riboside a trace nutrient in foods is a vitamin b3 with effects on energy metabolism and neuroprotection
Current Opinion in Clinical Nutrition and Metabolic Care, 2013Co-Authors: Yuling Chi, Anthony A. SauveAbstract:Purpose of reviewThis review focuses upon the biology and metabolism of a trace component in foods called nicotinamide Riboside. Nicotinamide Riboside is a precursor of nicotinamide adenine dinucleotide (NAD+), and is a source of Vitamin B3. Evidence indicates that nicotinamide Riboside has unique p
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Nicotinamide Riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection.
Current opinion in clinical nutrition and metabolic care, 2013Co-Authors: Yuling Chi, Anthony A. SauveAbstract:This review focuses upon the biology and metabolism of a trace component in foods called nicotinamide Riboside. Nicotinamide Riboside is a precursor of nicotinamide adenine dinucleotide (NAD), and is a source of Vitamin B3. Evidence indicates that nicotinamide Riboside has unique properties as a Vitamin B3. We review knowledge of the metabolism of this substance, as well as recent work suggesting novel health benefits that might be associated with nicotinamide Riboside taken in larger quantities than is found naturally in foods. Recent work investigating the effects of nicotinamide Riboside in yeast and mammals established that it is metabolized by at least two types of metabolic pathways. The first of these is degradative and produces nicotinamide. The second pathway involves kinases called nicotinamide Riboside kinases (Nrk1 and Nrk2, in humans). The likely involvement of the kinase pathway is implicated in the unique effects of nicotinamide Riboside in raising tissue NAD concentrations in rodents and for potent effects in eliciting insulin sensitivity, mitochondrial biogenesis, and enhancement of sirtuin functions. Additional studies with nicotinamide Riboside in models of Alzheimer's disease indicate bioavailability to brain and protective effects, likely by stimulation of brain NAD synthesis. Initial studies have clarified the potential for a lesser-known Vitamin B3 called nicotinamide Riboside that is available in selected foods, and possibly available to humans by supplements. It has properties that are insulin sensitizing, enhancing to exercise, resisting to negative effects of high-fat diet, and neuroprotecting.
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Syntheses of nicotinamide Riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells.
Journal of medicinal chemistry, 2007Co-Authors: Tianle Yang, Noel Yan-ki Chan, Anthony A. SauveAbstract:A new two-step methodology achieves stereoselective synthesis of β-nicotinamide Riboside and a series of related amide, ester, and acid nucleosides. Compounds were prepared through a triacetylated-nicotinate ester nucleoside, via coupling of either ethylnicotinate or phenylnicotinate with 1,2,3,5-tetra-O-acetyl-β-d-ribofuranose. Nicotinamide Riboside, nicotinic acid Riboside, O-ethylnicotinate Riboside, O-methylnicotinate Riboside, and several N-alkyl derivatives increased NAD+ concentrations from 1.2–2.7-fold in several mammalian cell lines. These findings establish bioavailability and potent effects of these nucleosides in stimulating the increase of NAD+ concentrations in mammalian cells.
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Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD
PLoS biology, 2007Co-Authors: Wolfram Tempel, Peter Belenky, Wael M. Rabeh, Katrina L. Bogan, Marzena Wojcik, Heather F. Seidle, Lyudmila Nedyalkova, Tianle Yang, Anthony A. Sauve, Hee-won ParkAbstract:The eukaryotic nicotinamide Riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide Riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide Riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide Riboside. Indeed, nicotinic acid Riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid Riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.
Vassilis Paschalis - One of the best experts on this subject based on the ideXlab platform.
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Nicotinamide Riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance.
Experimental physiology, 2018Co-Authors: Ioannis A. Kourtzidis, Aristidis S. Veskoukis, Nikos V. Margaritelis, Maria Tsantarliotou, Ioannis S. Vrabas, C. F. Dolopikou, A. N. Tsiftsis, Anastasios A. Theodorou, Ioannis Zervos, Vassilis PaschalisAbstract:What is the central question of this study? The aim was to investigate the potential metabolic and redox mechanisms that impaired exercise performance after 21 days of supplementation with 300 mg (kg body weight)-1 of nicotinamide Riboside in rats. What is the main finding and its importance? Nicotinamide Riboside disturbed energy and redox metabolism and impaired exercise performance in heathy rats. Exogenously administered redox agents in heathy populations might lead to adverse effects. Nicotinamide Riboside is a recently discovered form of vitamin B3 that can increase NAD(P) levels. NAD(P) plays key roles in energy metabolism, and its main function is the transfer of electrons in various cellular reactions. Research in aged or diseased mice reported that nicotinamide Riboside increases NAD(H) levels, reduces morbidity and improves health and muscle function. We have recently shown that in healthy young rats, chronic administration of nicotinamide Riboside marginally non-significantly decreased exercise performance by 35% (P = 0.071). As a follow-up to this finding, we analysed samples from these animals, in an attempt to reveal the potential mechanisms driving this adverse effect, focusing on redox homeostasis and bioenergetics. Thirty-eight Wistar rats were divided into four groups: control (n = 10), exercise (n = 9), nicotinamide Riboside (n = 10) and exercise plus nicotinamide Riboside (n = 9). Nicotinamide Riboside was administered for 21 days [300 mg (kg body weight)-1 daily]. At the end of administration, the exercise and the exercise plus nicotinamide Riboside groups performed an incremental swimming performance test until exhaustion. Nicotinamide Riboside supplementation increased the levels of NADPH in the liver (P = 0.050), increased the levels of F2 -isoprostanes in plasma (P = 0.047), decreased the activity of glutathione peroxidase (P = 0.017), glutathione reductase (P < 0.001) and catalase (P = 0.024) in erythrocytes, increased the level of glycogen in the liver (P < 0.001) and decreased the concentration of glucose (P = 0.016) and maximal lactate accumulation in plasma (P = 0.084). These findings support the prevailing idea that exogenously administered redox agents in heathy populations might lead to adverse effects and not necessarily to beneficial or neutral effects. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.
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Nicotinamide Riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance.
Experimental physiology, 2018Co-Authors: Ioannis A. Kourtzidis, Aristidis S. Veskoukis, Nikos V. Margaritelis, Maria Tsantarliotou, Ioannis S. Vrabas, C. F. Dolopikou, A. N. Tsiftsis, Anastasios A. Theodorou, Ioannis Zervos, Vassilis PaschalisAbstract:NEW FINDINGS What is the central question of this study? The aim was to investigate the potential metabolic and redox mechanisms that impaired exercise performance after 21 days of supplementation with 300 mg (kg body weight)-1 of nicotinamide Riboside in rats. What is the main finding and its importance? Nicotinamide Riboside disturbed energy and redox metabolism and impaired exercise performance in heathy rats. Exogenously administered redox agents in heathy populations might lead to adverse effects. ABSTRACT Nicotinamide Riboside is a recently discovered form of vitamin B3 that can increase NAD(P) levels. NAD(P) plays key roles in energy metabolism, and its main function is the transfer of electrons in various cellular reactions. Research in aged or diseased mice reported that nicotinamide Riboside increases NAD(H) levels, reduces morbidity and improves health and muscle function. We have recently shown that in healthy young rats, chronic administration of nicotinamide Riboside marginally non-significantly decreased exercise performance by 35% (P = 0.071). As a follow-up to this finding, we analysed samples from these animals, in an attempt to reveal the potential mechanisms driving this adverse effect, focusing on redox homeostasis and bioenergetics. Thirty-eight Wistar rats were divided into four groups: control (n = 10), exercise (n = 9), nicotinamide Riboside (n = 10) and exercise plus nicotinamide Riboside (n = 9). Nicotinamide Riboside was administered for 21 days [300 mg (kg body weight)-1 daily]. At the end of administration, the exercise and the exercise plus nicotinamide Riboside groups performed an incremental swimming performance test until exhaustion. Nicotinamide Riboside supplementation increased the levels of NADPH in the liver (P = 0.050), increased the levels of F2 -isoprostanes in plasma (P = 0.047), decreased the activity of glutathione peroxidase (P = 0.017), glutathione reductase (P
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The NAD(+) precursor nicotinamide Riboside decreases exercise performance in rats.
Journal of the International Society of Sports Nutrition, 2016Co-Authors: Ioannis A. Kourtzidis, Andreas T. Stoupas, Ioannis S. Gioris, Aristidis S. Veskoukis, Nikos V. Margaritelis, Maria Tsantarliotou, Ioannis Taitzoglou, Ioannis S. Vrabas, Vassilis Paschalis, Antonios KyparosAbstract:Nicotinamide adenine dinucleotide (NAD+) and its phosphorylated form (NADP+) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD+ and NADP+ precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide Riboside administration (an NAD+ precursor) affects exercise performance. Eighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide Riboside at a dose of 300 mg/kg body weight/day for 21 days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test. The nicotinamide Riboside group showed a tendency towards worse physical performance by 35 % compared to the control group at the final 10 % load (94 ± 53 s for the nicotinamide Riboside group and 145 ± 59 s for the control group; P = 0.071). Our results do not confirm the previously reported ergogenic effect of nicotinamide Riboside. The potentially negative effect of nicotinamide Riboside administration on physical performance may be attributed to the pleiotropic metabolic and redox properties of NAD+ and NADP+.
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the nad precursor nicotinamide Riboside decreases exercise performance in rats
Journal of The International Society of Sports Nutrition, 2016Co-Authors: Ioannis A. Kourtzidis, Andreas T. Stoupas, Ioannis S. Gioris, Aristidis S. Veskoukis, Nikos V. Margaritelis, Maria Tsantarliotou, Ioannis Taitzoglou, Ioannis S. Vrabas, Vassilis PaschalisAbstract:Nicotinamide adenine dinucleotide (NAD+) and its phosphorylated form (NADP+) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD+ and NADP+ precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide Riboside administration (an NAD+ precursor) affects exercise performance. Eighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide Riboside at a dose of 300 mg/kg body weight/day for 21 days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test. The nicotinamide Riboside group showed a tendency towards worse physical performance by 35 % compared to the control group at the final 10 % load (94 ± 53 s for the nicotinamide Riboside group and 145 ± 59 s for the control group; P = 0.071). Our results do not confirm the previously reported ergogenic effect of nicotinamide Riboside. The potentially negative effect of nicotinamide Riboside administration on physical performance may be attributed to the pleiotropic metabolic and redox properties of NAD+ and NADP+.
