Nicotinamide mononucleotide

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Nicotinamide mononucleotide
Nicotinamide mononucleotide.svg
Names
IUPAC name
3-Carbamoyl-1-[5-O-(hydroxyphosphinato)-β-D-ribofuranosyl]pyridinium
Preferred IUPAC name
[(2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
Other names
  • Nicotinamide ribonucleoside 5′-phosphate
  • Nicotinamide D-ribonucleotide
  • β-Nicotinamide ribose monophosphate
  • Nicotinamide nucleotide
Identifiers
3D model (JSmol)
3570187
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.012.851 Edit this at Wikidata
EC Number
  • 214-136-5
KEGG
UNII
  • 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/s1
    Key: DAYLJWODMCOQEW-TURQNECASA-N
  • c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)[O-])O)O)C(=O)N
Properties
C11H15N2O8P
Molar mass 334.221 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Nicotinamide mononucleotide (“NMN” and “β-NMN”) is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin.[1] In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH).[1] 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.[2] However, this observation has been challenged,[3] and the matter remains unsettled.[4]

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.[5][6] 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.[7] Dietary supplement companies have aggressively marketed NMN products, claiming those benefits.[8] However, no human studies to date have properly proven its anti-aging effects. Single-dose administration of up to 500 mg was shown safe in men in a study at Keio University School of Medicine, Shinjuku, Tokyo, Japan.[9] One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women,[10] while another found that it improved aerobic capacity in amateur runners.[11]

Molecular structure comparison of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) [12]

Nicotinamide riboside (NR) kinase enzymes are essential for exogenously administered utilization of NR and NMN.[13][14] Some research suggests when administered exogenously, NMN must be converted to NR in order to enter a cell and be re-phosphorylated back to NMN.[13]

The molecular structures of NMN and NR are similar. Compared to NR, NMN is monophosphorylated at the 5' position. Due to its larger size and charge, it is believed that NMN cannot cross cellular membranes and must convert to NR before entering cells, where NAD+ biosynthesis occurs. Otherwise, NMN would need to be transported into cells by a transporter specific for NMN, possibly Slc12a8.[12]

Both NR and NMN are vulnerable to extracellular degradation by CD38 enzyme,[14] which can be inhibited by compounds such as CD38-IN-78c.[15]

References[edit]

  1. ^ a b Bogan KL, Brenner C (2008). "Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition". Annual Review of Nutrition. 28: 115–30. doi:10.1146/annurev.nutr.28.061807.155443. PMID 18429699.
  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. ISSN 2090-1232. PMID 35499054. S2CID 238647478.
  8. ^ Stipp D (March 11, 2015). "Beyond Resveratrol: The Anti-Aging NAD Fad". Scientific American Blog Network.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ a b "NMN vs NR: The Differences Between These 2 NAD+ Precursors". www.nmn.com. Retrieved 2021-01-11.
  13. ^ a b Fletcher RS, Lavery GG (October 2018). "The emergence of the nicotinamide riboside kinases in the regulation of NAD+ metabolism". Journal of Molecular Endocrinology. 61 (3): R107–R121. doi:10.1530/JME-18-0085. PMC 6145238. PMID 30307159.
  14. ^ a b 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.
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