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Nicotinamide riboside

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Nicotinamide riboside
Names
Other names
1-(β-D-Ribofuranosyl)nicotinamide; N-Ribosylnicotinamide
Identifiers
ChEBI
Properties
C11H15N2O5+
Molar mass 255.25 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.[1][2]

Discovery of NR as a bacterial NAD precursor

NR was first described as a growth factor, termed Factor V, for Haemophilus influenza, a bacterium that lives in and depends on blood. Factor V, purified from blood was shown to exist in three forms: NAD+, NMN and NR. NR was the compound that led to the most rapid growth of this bacterium.[3] Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.[4]

Discovery of NR as a eukaryotic NAD precursor vitamin

In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase,[5] which led several groups to probe yeast NAD+ metabolism for genes and enzymes that might regulate lifespan. Biosynthesis of NAD+ in yeast was thought to flow exclusively through NAMN.[6][7][8][9][10]

Surprisingly, when NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by these enzymes in vitro and in vivo. They also demonstrated that NR is a natural product, the so-called hidden vitamin found in cow's milk.[11][12]

Potential applications for NR in human health

High dose nicotinic acid is used as an agent that elevates high-density lipoprotein cholesterol, lowers low-density lipoprotein cholesterol and lower free fatty acids through a mechanism that is not completely understood. It was suggested that nicotinamide riboside might possess such an activity by elevating NAD in the cells responsible for reverse cholesterol transport.[4] An experiment with mice on high fat diet appears to support the potential of treatment or prevention of dyslipidemia with nicotinamide riboside.[13]

The discovery that the Wallerian degeneration slow gene encodes a protein fusion with NMN adenylyltransferase 1 indicated that increased NAD+ precursor supplementation might oppose neurodegenerative processes.[4] NR blocks degeneration of surgically severed dorsal root ganglion neurons ex vivo [14] and protects against noise-induced hearing loss in living mice.[15][16]

Commercialization of NR

Publicly traded company ChromaDex acquired intellectual property on uses and synthesis of NR Chloride from Dartmouth College, Cornell University and Washington University and began distributing NR as NIAGEN™ in 2013.[17]

See also

NIH researchers find potential target for reducing obesity-related inflammation
Beyond Resveratrol: The Anti-Aging NAD Fad
Mechanism of Nicotinamide Riboside as an Aid to Weight Loss
Increasing NAD+ availability in skeletal muscle to augment energy metabolism

References

  1. ^ Bogan, K.L., Brenner, C. (2008). "Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition". Annu. Rev. Nutr. 28: 115–130. doi:10.1146/annurev.nutr.28.061807.155443.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Chi Y, Sauve AA (November 2013). "Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection". Curr Opin Clin Nutr Metab Care. 16 (6): 657–61. doi:10.1097/MCO.0b013e32836510c0. PMID 24071780.
  3. ^ Gingrich, W (1944). "Codehydrogenase I and other pyridinium compounds as V factor for Haemophilus influenzae and Haemophilus parainfluenzae". J. Bacteriol. 47: 535–550.
  4. ^ a b c Belenky, P.; et al. (2007). "NAD+ Metabolism in Health and Disease". Trends in Biochemical Sciences. 32: 12–19. doi:10.1016/j.tibs.2006.11.006. PMID 17161604. {{cite journal}}: Explicit use of et al. in: |author= (help)
  5. ^ Imai, S.; et al. (2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase". Nature. 403 (6771): 795–800.
  6. ^ Panozzo, C.; et al. (2002). "Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae". FEBS Lett. 517: 97–102. doi:10.1016/s0014-5793(02)02585-1.
  7. ^ Sandmeier; et al. (2002). "Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD Salvage Pathway". Genetics. 160: 877–889. {{cite journal}}: Explicit use of et al. in: |author= (help)
  8. ^ Bitterman; et al. (2002). "Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1". J. Biol. Chem. 277: 45099–45107. doi:10.1074/jbc.m205670200. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: unflagged free DOI (link)
  9. ^ Anderson; et al. (2003). "Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae". Nature. 423: 181–185. doi:10.1038/nature01578. PMID 12736687. {{cite journal}}: Explicit use of et al. in: |author= (help)
  10. ^ Gallo; et al. (2004). "Nicotinamide clearance by pnc1 directly regulates sir2-mediated silencing and longevity". Mol. Cel. Biol. 24: 1301–1312. doi:10.1128/mcb.24.3.1301-1312.2004.
  11. ^ Bieganowki, P. and Brenner, C. (2004). "Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans". Cell. 117: 495–502. doi:10.1016/s0092-8674(04)00416-7.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Hautkooper, R.H.; et al. (2012). "Sirtuins as regulators of metabolism and healthspan". Nat. Rev. Mol. Cell. Bill. 13: 225–238. doi:10.1038/nrm3293.
  13. ^ Canto, C.; et al. (2012). "The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity". Cell Metabolism. 15: 838–847. doi:10.1016/j.cmet.2012.04.022. {{cite journal}}: Explicit use of et al. in: |author= (help)
  14. ^ Sasaki, Y.; et al. (2006). "Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy". J. Neurosci. 26: 8484–8491. doi:10.1523/jneurosci.2320-06.2006. {{cite journal}}: Explicit use of et al. in: |author= (help)
  15. ^ Brown, K.D.; et al. (2014). "Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss". Cell Metab. 20: 1059–1068. doi:10.1016/j.cmet.2014.11.003. {{cite journal}}: Explicit use of et al. in: |author= (help)
  16. ^ Brenner, C. (2014). "Boosting NAD to Spare Hearing". Cell Metab. 20: 926–927. doi:10.1016/j.cmet.2014.11.015.
  17. ^ "ChromaDex Introduces Niagen". Retrieved 2014-04-23.
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