Nicotinamide riboside

Nicotinamide riboside
Names
Other names
1-(β-D-Ribofuranosyl)nicotinamide; N-Ribosylnicotinamide
Identifiers
1341-23-7
ChEBI CHEBI:15927
PubChem 439924
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.

Discovery

Bacterial NAD precursor

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.[6] Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.[7]

Eukaryotic NAD precursor vitamin

In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase,[8] 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.[9][10][11][12][13]

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.[14][15] In humans, NR is orally available and produces safe, dose-dependent increases in blood NAD+ metabolism.[16][17]

Potential applications 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.[7] An experiment with mice on high fat diet appears to support the potential of treatment or prevention of dyslipidemia with nicotinamide riboside.[18]

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.[7] NR blocks degeneration of surgically severed dorsal root ganglion neurons ex vivo[19] and protects against noise-induced hearing loss in living mice.[20][21]

Nicotinamide riboside prevents muscle, neural and melanocyte stem cell senescence.[22] Increased muscular regeneration in mice has been observed after treatment with nicotinamide riboside, leading to speculation that it might improve regeneration of organs such as the liver, kidney, and heart.[23] Nicotinamide riboside also lowers blood glucose and fatty liver in prediabetic and type 2 diabetic models while preventing the development of diabetic peripheral neuropathy.[24]

Commercialization

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.[25] A clinical trial demonstrated safe oral availability to increase human NAD+ metabolism.[26][27] ChromaDex began another clinical trial to examine the benefits if taken daily for eight consecutive weeks.[28]

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. doi:10.1097/MCO.0b013e32836510c0. PMID 24071780.
  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. doi:10.1074/jbc.M110.213298. ISSN 0021-9258.
  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. doi:10.1016/S0092-8674(04)00416-7. PMID 15137942.
  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. doi:10.1016/j.cell.2007.03.024. PMID 17482543.
  6. ↑ Gingrich, W (1944). "Codehydrogenase I and other pyridinium compounds as V factor for Haemophilus influenzae and Haemophilus parainfluenzae". J. Bacteriol. 47: 535–550.
  7. 1 2 3 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.
  8. ↑ Imai, S.; et al. (2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase". Nature. 403 (6771): 795–800.
  9. ↑ 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.
  10. ↑ Sandmeier; et al. (2002). "Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD Salvage Pathway". Genetics. 160: 877–889.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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. doi:10.1016/s0092-8674(04)00416-7.
  15. ↑ 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.
  16. ↑ "https://www.sciencedaily.com/releases/2016/10/161010135418.htm". www.sciencedaily.com. Retrieved 2016-10-11. External link in |title= (help)
  17. ↑ Trammell, S.A.J.; et al. (2016). "Nicotinamide riboside is uniquely and orally bioavailable in mice and humans". Nat. Comm.: 12948. doi:10.1038/ncomms12948.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ Brenner, C. (2014). "Boosting NAD to Spare Hearing". Cell Metab. 20: 926–927. doi:10.1016/j.cmet.2014.11.015.
  22. ↑ Zhang, Hongbo; Ryu, Dongryeol; Wu, Yibo; Gariani, Karim; Wang, Xu; Luan, Peiling; D’Amico, Davide; Ropelle, Eduardo R.; Lutolf, Matthias P. (2016-04-28). "NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice". Science: aaf2693. doi:10.1126/science.aaf2693. ISSN 0036-8075. PMID 27127236.
  23. ↑ Vitamin stops the aging process of organs, Science Daily, April 28, 2016. See also David W. Frederick et. al., Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle, Cell Metabolism, Volume 24, Issue 2, p269–282, 9 August 2016.
  24. ↑ Trammell, SAJ, Weidemann, BJ, Chadda, A, Yorek, MS, Holmes, A, Coppey, LJ, Obrosov, A, Kardon, RH, Yorek, MA, Brenner, C (2016). "Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice". Sci. Reports. 6: 26933. doi:10.1038/srep26933.
  25. ↑ "ChromaDex Introduces Niagen". Retrieved 2014-04-23.
  26. ↑ Trammell, S.A.J.; et al. (2016). "Nicotinamide riboside is uniquely and orally bioavailable in mice and humans". Nat. Comm.: 12948. doi:10.1038/ncomms12948.
  27. ↑ Inc., ChromaDex,. "Results from First Human Clinical Study Demonstrate ChromaDex's NIAGEN(R) Nicotinamide Riboside Effectively Increases the Co-enzyme NAD+ and is Safe". GlobeNewswire News Room. Retrieved 2016-03-22.
  28. ↑ Inc., ChromaDex,. "ChromaDex Initiates Second Human Clinical Study on NIAGEN® -The World's First and Only Commercially Available Form of Nicotinamide Riboside (NR)". GlobeNewswire News Room. Retrieved 2016-03-22.

Further reading

This article is issued from Wikipedia - version of the 10/30/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.