Wikipedia

Dihydronicotinamide mononucleotide

(Redirected from NMNH (Dihydronicotinamide Mononucleotide))

NMNH (Dihydronicotinamide mononucleotide), also known as reduced nicotinamide mononucleotide.[1] Both NMNH and NMN have been scientifically shown to enhance NAD+ levels in the body.[1] NAD+ is a universal coenzyme that plays vital roles in nearly all living organisms functioning in various biological processes such as metabolism, cell signaling, gene regulation, and DNA repair.[2][3] It has been observed that a decline in NAD+ levels is linked to typical signs of aging and could potentially be linked to various age-related diseases, including metabolic diseases, cancer, and neurodegenerative diseases.

Dihydronicotinamide mononucleotide
Names
IUPAC name
[(2R,3S,4R,5R)-5-(3-Carbamoyl-4H-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Other names
Reduced nicotinamide mononucleotide
Identifiers
3D model (JSmol)
Abbreviations NMNH
ChEBI
ChEMBL
ChemSpider
KEGG
  • InChI=1S/C11H17N2O8P/c12-10(16)6-2-1-3-13(4-6)11-9(15)8(14)7(21-11)5-20-22(17,18)19/h1,3-4,7-9,11,14-15H,2,5H2,(H2,12,16)(H2,17,18,19)/t7-,8-,9-,11-/m1/s1
    Key: XQHMUSRSLNRVGA-TURQNECASA-N
  • C1C=CN(C=C1C(=O)N)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)O)O)O
Properties
C11H17N2O8P
Molar mass 336.237 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

NAD+ Precursors

The members of the NAD+ precursor family include tryptophan (Trp), nicotinic acid (NA), nicotinamide (NAM), nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), reduced nicotinamide ribose (NRH)[4] and reduced nicotinamide mononucleotide (NMNH)[5] of these, the majority are logically vitamin B substances or their congeners[6][7] Based on the bioavailability of its precursors, there are three pathways for the synthesis of NAD+ in cells.[6][8]

De Novo Biosynthesis Pathway: Convert NAD+ from tryptophan through the kynurenine pathway.[9][10][7]

Preiss-Handler Pathway: These include nicotinamide nucleotide transhydrogenase, which synthesizes NAD+ from nicotinic acid (NA).[9][10][7]

Salvage Pathway: biotransforms NAM, NR, and NMN into NAD+.[9][10]

Toxicity

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A group of researchers from Tsinghua University considered the effect of NMNH on C57BL/6J male mice when they injected the animal with 50, 100, 500, or 1000 mg/kg NMNH intraperitoneally every other day for a week.[10] This research indicates that serum levels of ALT and AST were not high thus leading to no evidence showing that NMNH is toxic to the liver when taken in higher dosages.[10]

Assessment

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There is no public information on whether NMNH occurs naturally in plants and animals, although traces of NMNH may be present in the human body.[11]

Uses

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NMNH can act as a potent NAD+ enhancer, potentially leading to a new generation of highly efficient NAD+-boosting molecules that could overcome the limitations of current NAD+ enhancers. [18] NMNH protects tubular epithelial cells against hypoxia/reoxygenation injury by enhancing repair.[8]

Absorption and metabolism

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NMNH has proven to be a more effective NAD+ enhancer than NMN, achieving a 5-fold increase in NAD+ levels and sustaining elevated levels for six hours while maintaining high levels for up to 24 hours.[1] NMNH treatment leads to a similar trend in NAD+ and NADH biosynthesis as NMN treatment, implying a shared pathway.[5] However, NMNH was shown to inhibit the endogenous synthesis of NMN by blocking the action of nicotinamide phosphoribosyl transferase (NAMPT)[5] This inhibition suggests that NMNH may be more effective than NMN in directly stimulating NAD+ production.[5]

References

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  1. ^ a b c Zapata-Pérez, Rubén; Tammaro, Alessandra; Schomakers, Bauke V.; Scantlebery, Angelique M. L.; Denis, Simone; Elfrink, Hyung L.; Giroud-Gerbetant, Judith; Cantó, Carles; López-Leonardo, Carmen; McIntyre, Rebecca L.; van Weeghel, Michel; Sánchez-Ferrer, Álvaro; Houtkooper, Riekelt H. (April 2021). "Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice". FASEB Journal. 35 (4): e21456. doi:10.1096/fj.202001826R. ISSN 1530-6860. PMID 33724555.
  2. ^ Nadeeshani, Harshani; Li, Jinyao; Ying, Tianlei; Zhang, Baohong; Lu, Jun (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 2090-1224. PMC 9039735. PMID 35499054.
  3. ^ Benjamin, Candace; Crews, Rebecca (June 2024). "Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications". Metabolites. 14 (6): 341. doi:10.3390/metabo14060341. ISSN 2218-1989. PMC 11205942. PMID 38921475.
  4. ^ Giroud-Gerbetant, Judith; Joffraud, Magali; Giner, Maria Pilar; Cercillieux, Angelique; Bartova, Simona; Makarov, Mikhail V.; Zapata-Pérez, Rubén; Sánchez-García, José L.; Houtkooper, Riekelt H.; Migaud, Marie E.; Moco, Sofia; Canto, Carles (2019-12-01). "A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor". Molecular Metabolism. 30: 192–202. doi:10.1016/j.molmet.2019.09.013. ISSN 2212-8778. PMC 6807296. PMID 31767171.
  5. ^ a b c d Liu, Yan; Luo, Chengting; Li, Ting; Zhang, Wenhao; Zong, Zhaoyun; Liu, Xiaohui; Deng, Haiteng (2021-05-07). "Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhances NAD+ and Suppresses Glycolysis, the TCA Cycle, and Cell Growth". Journal of Proteome Research. 20 (5): 2596–2606. doi:10.1021/acs.jproteome.0c01037. ISSN 1535-3907. PMID 33793246.
  6. ^ a b Verdin, Eric (2015-12-04). "NAD⁺ in aging, metabolism, and neurodegeneration". Science. 350 (6265): 1208–1213. doi:10.1126/science.aac4854. ISSN 1095-9203. PMID 26785480.
  7. ^ a b c Poljsak, B.; Milisav, I. (2018-09-01). "Vitamin B3 forms as precursors to NAD+: Are they safe?". Trends in Food Science & Technology. 79: 198–203. doi:10.1016/j.tifs.2018.07.020. ISSN 0924-2244.
  8. ^ a b Billingham, Leah K.; Chandel, Navdeep S. (April 2019). "NAD-biosynthetic pathways regulate innate immunity". Nature Immunology. 20 (4): 380–382. doi:10.1038/s41590-019-0353-x. ISSN 1529-2916. PMID 30858621.
  9. ^ a b c Yoshino, Jun; Baur, Joseph A.; Imai, Shin-Ichiro (2018-03-06). "NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR". Cell Metabolism. 27 (3): 513–528. doi:10.1016/j.cmet.2017.11.002. ISSN 1932-7420. PMC 5842119. PMID 29249689.
  10. ^ a b c d e Misiak, Magdalena; Vergara Greeno, Rebeca; Baptiste, Beverly A.; Sykora, Peter; Liu, Dong; Cordonnier, Stephanie; Fang, Evandro F.; Croteau, Deborah L.; Mattson, Mark P.; Bohr, Vilhelm A. (February 2017). "DNA polymerase β decrement triggers death of olfactory bulb cells and impairs olfaction in a mouse model of Alzheimer's disease". Aging Cell. 16 (1): 162–172. doi:10.1111/acel.12541. ISSN 1474-9726. PMC 5242308. PMID 27686631.
  11. ^ Giner, Maria Pilar; Christen, Stefan; Bartova, Simona; Makarov, Mikhail V.; Migaud, Marie E.; Canto, Carles; Moco, Sofia (2021-09-30). "A Method to Monitor the NAD+ Metabolome-From Mechanistic to Clinical Applications". International Journal of Molecular Sciences. 22 (19): 10598. doi:10.3390/ijms221910598. ISSN 1422-0067. PMC 8508997. PMID 34638936.
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