Nicotinamide riboside

Nicotinamide riboside
Names
Other names
1-(β-D-Ribofuranosyl)nicotinamide; N-Ribosylnicotinamide
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
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).
Infobox references

Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.[1][2] According to the peer-reviewed literature,[3] NR was discovered as a human vitamin precursor of NAD+ in 2004[4] and as a sirtuin-activating compound[5] in 2007 by Charles Brenner.

Toxicity

In 2016 the FDA granted generally recognized as safe (GRAS) status for NR as a food ingredient in enhanced water products, protein shakes, nutrition bars, gum and chews at no more than 0.027% of NR by weight.[6] The NOAEL and LOAEL in rodents are 300 and 1000 mg/kg/day respectively.[6]:2–3

Chemistry

While the molecular weight of nicotinamide riboside is 255.25 g/mol,[7] that of its chloride salt is 290.70 g/mol.[6]:7 As such, 100 mg of nicotinamide riboside chloride provides 88 mg of nicotinamide riboside.

History

NR was first described in 1944 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.[8] Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.[9]

In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase,[10] 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 (nicotinic acid mononucleotide).[11][12][13][14][15]

Surprisingly, when NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these Dartmouth College investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by nicotinamide riboside kinases in vitro and in vivo. They also demonstrated that NR is a natural product, the so-called hidden vitamin found in cow's milk.[16][17]

ChromaDex acquired intellectual property on uses and synthesis of NR from Dartmouth College, Cornell University, and Washington University and began distributing NR as Niagen in 2013.[18] In 2015, ChromaDex received New Dietary Ingredient (NDI) status for Niagen from the U.S. Food and Drug Administration (FDA)[19]

Research

Nicotinamide riboside has been studied in models of hypercholesterolemia and neurodegenerative processes.[9]

See also

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.
  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. PMID 24071780. doi:10.1097/MCO.0b013e32836510c0.
  3. ↑ Nikiforov, Andrey; Dölle, Christian; Niere, Marc; Ziegler, Mathias (2011-06-17). "Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells FROM ENTRY OF EXTRACELLULAR PRECURSORS TO MITOCHONDRIAL NAD GENERATION". Journal of Biological Chemistry. 286 (24): 21767–21778. ISSN 0021-9258. PMC 3122232 Freely accessible. PMID 21504897. doi:10.1074/jbc.M110.213298.
  4. ↑ Bieganowski, P; 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 (4): 495–502. PMID 15137942. doi:10.1016/S0092-8674(04)00416-7.
  5. ↑ Belenky, P; et al. (2007). "Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+". Cell. 129 (3): 473–484. PMID 17482543. doi:10.1016/j.cell.2007.03.024.
  6. 1 2 3 "Spherix/Chromadex GRAS submission" (PDF). March 8, 2016. See FDA GRAS index page: "GRAS Notice (GRN) No. 635".
  7. ↑ "Nicotinamide Riboside".
  8. ↑ Gingrich, W (1944). "Codehydrogenase I and other pyridinium compounds as V factor for Haemophilus influenzae and Haemophilus parainfluenzae". J. Bacteriol. 47: 535–550.
  9. 1 2 Belenky, P. et. al. (2007). "NAD+ Metabolism in Health and Disease". Trends in Biochemical Sciences. 32: 12–19. PMID 17161604. doi:10.1016/j.tibs.2006.11.006.
  10. ↑ Imai, S.; et al. (2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase". Nature. 403 (6771): 795–800.
  11. ↑ 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.
  12. ↑ Sandmeier; et al. (2002). "Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD Salvage Pathway". Genetics. 160: 877–889.
  13. ↑ 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. PMID 12297502. doi:10.1074/jbc.m205670200.
  14. ↑ Anderson; et al. (2003). "Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae". Nature. 423: 181–185. PMC 4802858 Freely accessible. PMID 12736687. doi:10.1038/nature01578.
  15. ↑ 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.
  16. ↑ Bieganowki, P. & 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. PMID 15137942. doi:10.1016/s0092-8674(04)00416-7.
  17. ↑ 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.
  18. ↑ "Press Release: ChromaDex Introduces Niagen". Chromadex via PR Newswire. May 29, 2013.
  19. ↑ "Press Release: ChromaDex receives NDI status from FDA". ChromaDex via Globe Newswire. November 16, 2015.

Further reading

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