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Nicotinamide mononucleotide

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Nicotinamide mononucleotide
Names
IUPAC name 3-Carbamoyl-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium
Systematic IUPAC name methyl hydrogen phosphate
Other names
  • Nicotinamide ribonucleoside 5′-phosphate
  • Nicotinamide D-ribonucleotide
  • β-Nicotinamide ribose monophosphate
  • Nicotinamide nucleotide
Identifiers
CAS Number
3D model (JSmol)
Beilstein Reference 3570187
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.012.851 Edit this at Wikidata
EC Number
  • 214-136-5
KEGG
PubChem CID
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C11H15N2O8P/c12-10(16)6-2-1-3-13(4-6)11-9(15)8(14)7(21-11)5-20-22(17,18)19/h1-4,7-9,11,14-15H,5H2,(H3-,12,16,17,18,19)/t7-,8-,9-,11-/m1/s1Key: DAYLJWODMCOQEW-TURQNECASA-N
SMILES
  • c1cc(c(c1)2(((O2)COP(=O)(O))O)O)C(=O)N
Properties
Chemical formula C11H15N2O8P
Molar mass 334.221 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

Nicotinamide mononucleotide ("NMN" and "β-NMN") is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin. In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH). In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (NAD+) through the Slc12a8 transporter. However, this observation has been challenged, and the matter remains unsettled.

Because NADH is a cofactor for processes inside mitochondria, for sirtuins and PARP, NMN has been studied in animal models as a potential neuroprotective and anti-aging agent. The reversal of aging at the cellular level by inhibiting mitochondrial decay in presence of increased levels of NAD+ makes it popular among anti-aging products. Dietary supplement companies have aggressively marketed NMN products, claiming those benefits. However, no human studies to date have properly proven its anti-aging effects with proposed health benefits only suggested through research done in vitro or through animal models. Single-dose administration of up to 500 mg was shown safe in men in a study at Keio University. One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women, while another found that it improved aerobic capacity in amateur runners. A 2023 clinical trial showed that NMN improves performance on a six-minute walking test and a subjective general health assessment.

NMN is vulnerable to extracellular degradation by CD38 enzyme, which can be inhibited by compounds such as CD38-IN-78c.

Dietary sources

NMN is found in fruits and vegetables such as edamame, broccoli, cabbage, cucumber and avocado at a concentration of about 1 mg per 100g, making these natural sources impractical to acquire the quantities needed to accomplish the dosing currently being investigated for NMN as a pharmaceutical.

Production

Production of nicotinamide mononucleotide has been redacted since the latter half of 2022 by the FDA because it is under investigation as a pharmaceutical drug.

Different expressions of NMN across human organs

The synthesizing enzymes and consumption enzymes of NMN also exhibit tissue specificity: NMN is widely distributed in tissues and organs throughout the body and has been present in various cells since embryonic development.

Potential benefits and risks

NMN is a precursor for NAD biosynthesis, and NMN dietary supplementation has been demonstrated to increase NAD concentration and thus has the potential to mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration and inflammatory responses. The potential benefits and risks of NMN supplementation, as of 2023, are currently under investigation.

Certain enzymes are sensitive to the intracellular NMN/NAD ratio, such as SARM1, a protein responsible for initiating cellular degeneration pathways such as MAP kinase and inducing axonal loss and neuronal death. NMNAT is an enzyme with neurorescuing properties that functions to deplete NMN and produce NAD, attenuating SARM1 activity and aiding neuronal survival in-vitro, an effect that is reversed by applying exogenous NMN which promptly resumed axon destruction. The similar molecule nicotinic acid mononucleotide (NaMN) opposes the activating effect of NMN on SARM1, and is a neuroprotector.

References

  1. ^ Roger Lee, Roger (2023). "Different Expressions of NMN Across Human Organs". American Journal of Sociology – via Frank Lee.
  2. Grozio, A; Mills, KF; Yoshino, J; Bruzzone, S; Sociali, G; Tokizane, K; Lei, HC; Cunningham, R; Sasaki, Y; Migaud, ME; Imai, SI (January 2019). "Slc12a8 is a nicotinamide mononucleotide transporter". Nature Metabolism. 1 (1): 47–57. doi:10.1038/s42255-018-0009-4. PMC 6530925. PMID 31131364.
  3. Schmidt, MS; Brenner, C (July 2019). "Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter". Nature Metabolism. 1 (7): 660–661. doi:10.1038/s42255-019-0085-0. PMID 32694648. S2CID 203899191.
  4. Chini, CCS; Zeidler, JD; Kashyap, S; Warner, G; Chini, EN (1 June 2021). "Evolving concepts in NAD metabolism". Cell Metabolism. 33 (6): 1076–1087. doi:10.1016/j.cmet.2021.04.003. PMC 8172449. PMID 33930322.
  5. Brazill JM, Li C, Zhu Y, Zhai RG (June 2017). "+ synthase... It's a chaperone... It's a neuroprotector". Current Opinion in Genetics & Development. 44: 156–162. doi:10.1016/j.gde.2017.03.014. PMC 5515290. PMID 28445802.
  6. Mills, Kathryn F.; Yoshida, Shohei; Stein, Liana R.; Grozio, Alessia; Kubota, Shunsuke; Sasaki, Yo; Redpath, Philip; Migaud, Marie E.; Apte, Rajendra S.; Uchida, Koji; Yoshino, Jun; Imai, Shin-Ichiro (13 December 2016). "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice". Cell Metabolism. 24 (6): 795–806. doi:10.1016/j.cmet.2016.09.013. PMC 5668137. PMID 28068222.
  7. Nadeeshani, Harshani; Li, Jinyao; Ying, Tianlei; Zhang, Baohong; Lu, Jun (1 March 2022). "Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns". Journal of Advanced Research. 37: 267–278. doi:10.1016/j.jare.2021.08.003. hdl:10292/15010. ISSN 2090-1232. PMC 9039735. PMID 35499054. S2CID 238647478.
  8. Stipp D (March 11, 2015). "Beyond Resveratrol: The Anti-Aging NAD Fad". Scientific American Blog Network.
  9. Nadeeshani, Harshani; Li, Jinyao; Ying, Tianlei; Zhang, Baohong; Lu, Jun (2022-03-01). "Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns". Journal of Advanced Research. 37: 267–278. doi:10.1016/j.jare.2021.08.003. ISSN 2090-1232. PMC 9039735. PMID 35499054.
  10. Irie, Junichiro; Inagaki, Emi; Fujita, Masataka; Nakaya, Hideaki; Mitsuishi, Masanori; Yamaguchi, Shintaro; Yamashita, Kazuya; Shigaki, Shuhei; Ono, Takashi; Yukioka, Hideo; Okano, Hideyuki (2020). "Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men". Endocrine Journal. 67 (2): 153–60. doi:10.1507/endocrj.EJ19-0313. ISSN 0918-8959. PMID 31685720.
  11. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, et al. (June 2021). "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women". Science. 372 (6547): 1224–29. doi:10.1126/science.abe9985. PMC 8550608. PMID 33888596.
  12. Liao, B; Zhao, Y; Wang, D; Zhang, X; Hao, X; Hu, M (2021). ""Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study"". Journal of the International Society of Sports Nutrition. 18 (1): 54. doi:10.1186/s12970-021-00442-4. PMC 8265078. PMID 34238308.
  13. Yi Lin; et al. (Feb 2023). "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial". Geroscience. 45 (1): 29–43. doi:10.1007/s11357-022-00705-1. PMC 9735188. PMID 36482258.
  14. Cambronne XA, Kraus WL (October 2020). "+ Synthesis and Functions in Mammalian Cells". Trends in Biochemical Sciences. 45 (10): 858–73. doi:10.1016/j.tibs.2020.05.010. PMC 7502477. PMID 32595066.
  15. Tarragó MG, Chini CC, Kanamori KS, Warner GM, Caride A, et al. (May 2018). "A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline". Cell Metab. 27 (5): 1081–95.e10. doi:10.1016/j.cmet.2018.03.016. PMC 5935140. PMID 29719225.
  16. Mills, KF; Yoshida, S; Stein, LR; Grozio, A; Kubota, S; Sasaki, Y; Redpath, P; Migaud, ME; Apte, RS; Uchida, K; Yoshino, J; Imai, SI (13 December 2016). "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice". Cell Metabolism. 24 (6): 795–806. doi:10.1016/j.cmet.2016.09.013. PMC 5668137. PMID 28068222.
  17. Ryan, Finn (2016-12-06). "5 Anti-Aging Food Types You Should Already Be Eating". Bicycling. Retrieved 2022-01-20.
  18. "Scientists identify new fuel-delivery route for cells". Washington University School of Medicine. 2019-01-07. Retrieved 2022-01-20.
  19. nutraingredients-usa.com/Article/2023/02/16/Amazon-removing-NMN-dietary-supplements-citing-FDA-actions
  20. ^ "FDA Halts NMN Supplement Approval, Citing Pharmaceutical Potential".
  21. ^ Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J (November 2023). "The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update". Adv Nutr. 14 (6): 1416–35. doi:10.1016/j.advnut.2023.08.008. PMC 10721522. PMID 37619764.
  22. Figley, Matthew D.; Gu, Weixi; Nanson, Jeffrey D.; Shi, Yun; Sasaki, Yo; Cunnea, Katie; Malde, Alpeshkumar K.; Jia, Xinying; Luo, Zhenyao; Saikot, Forhad K.; Mosaiab, Tamim; Masic, Veronika; Holt, Stephanie; Hartley-Tassell, Lauren; McGuinness, Helen Y.; Manik, Mohammad K.; Bosanac, Todd; Landsberg, Michael J.; Kerry, Philip S.; Mobli, Mehdi; Hughes, Robert O.; Milbrandt, Jeffrey; Kobe, Bostjan; DiAntonio, Aaron; Ve, Thomas (7 April 2021). "SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration". Neuron. 109 (7): 1118–1136.e11. doi:10.1016/j.neuron.2021.02.009. PMC 8174188. PMID 33657413.
  23. ^ Di Stefano, M; Nascimento-Ferreira, I; Orsomando, G; Mori, V; Gilley, J; Brown, R; Janeckova, L; Vargas, M E; Worrell, L A; Loreto, A; Tickle, J; Patrick, J; Webster, J R M; Marangoni, M; Carpi, F M; Pucciarelli, S; Rossi, F; Meng, W; Sagasti, A; Ribchester, R R; Magni, G; Coleman, M P; Conforti, L (April 2015). "A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration". Cell Death and Differentiation. 22 (5): 731–742. doi:10.1038/cdd.2014.164. hdl:11581/387761. PMC 4392071. PMID 25323584.
  24. Zhao, Zhi Ying; Xie, Xu Jie; Li, Wan Hua; Liu, Jun; Chen, Zhe; Zhang, Ben; Li, Ting; Li, Song Lu; Lu, Jun Gang; Zhang, Liangren; Zhang, Li-he; Xu, Zhengshuang; Lee, Hon Cheung; Zhao, Yong Juan (4 May 2019). "A Cell-Permeant Mimetic of NMN Activates SARM1 to Produce Cyclic ADP-Ribose and Induce Non-apoptotic Cell Death". iScience. 15: 452–466. doi:10.1016/j.isci.2019.05.001. PMC 6531917. PMID 31128467.
  25. Brazill, Jennifer M.; Li, Chong; Zhu, Yi; Zhai, R. Grace (26 April 2017). "NMNAT: It's an NAD+ Synthase... It's a Chaperone... It's a Neuroprotector". Current Opinion in Genetics & Development. 44: 156–162. doi:10.1016/j.gde.2017.03.014. PMC 5515290. PMID 28445802.
  26. Gerdts, Josiah; Summers, Daniel W.; Milbrandt, Jeffrey; DiAntonio, Aaron (3 February 2016). "Axon self destruction: new links among SARM1, MAPKs, and NAD+ metabolism". Neuron. 89 (3): 449–460. doi:10.1016/j.neuron.2015.12.023. PMC 4742785. PMID 26844829.
  27. Sasaki, Yo; Zhu, Jian; Shi, Yun; Gu, Weixi; Kobe, Bostjan; Ve, Thomas; DiAntonio, Aaron; Milbrandt, Jeffrey (November 2021). "Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection". Experimental Neurology. 345: 113842. doi:10.1016/j.expneurol.2021.113842. hdl:10072/407468. PMC 8571713. PMID 34403688.
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