Nicotinamide Mononucleotide

Application and synthesis methods of β - nicotinamide mononucleotide
character
The appearance of β - nicotinamide mononucleotide is white to slightly yellow, and it is a crystalline powder with no obvious odor.
brief introduction
Nicotinamide mononucleotide, also known as β - nicotinamide mononucleotide (NMN), is a synthetic substrate for coenzyme I and is also used in anti-aging research. Research has shown that β - NMN can also regulate insulin secretion and affect mRNA expression levels. β - NMN has broad application prospects in the field of medical treatment.
β - nicotinamide mononucleotide is a product of the extracellular nicotinamide phosphoribosyltransferase (eNAMPT) reaction and a key NAD+intermediate. It improves glucose tolerance by restoring NAD+levels in HFD induced T2D mice. It also enhances liver insulin sensitivity and partially restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm through SIRT1 activation.

source
Nicotinamide mononucleotide, or NMN for short, is an inherent substance in human body, and is also rich in some fruits and vegetables, including broccoli, cabbage, etc.

purpose
In mammals, β - nicotinamide mononucleotide is generated by nicotinamide (Nam) catalyzed by Nampt (a protease in the body), and then nicotinamide mononucleotide is converted to NAD+catalyzed by nicotinamide mononucleotide adenyltransferase. Nicotinamide mononucleotide is a direct way to supplement NAD+. Nicotinamide mononucleotide significantly enhances the repair ability of intracellular DNA damage, ultimately achieving the effect of reversing aging.
Nicotinamide mononucleotide is converted into nicotinamide adenine dinucleotide (NAD), an essential substance for energy metabolism in the body. In mouse experiments, it was confirmed that nicotinamide mononucleotide can activate a gene called acetylase in the body, so as to play a role in prolonging life and treating diabetes. NAD is a substance that the human body can originally produce, and research has shown that the NAD content in the body decreases with age.

application
β - nicotinamide mononucleotide is a precursor substance of NAD+, a cofactor of longevity protein in the human body. NAD+is an important coenzyme in the tricarboxylic acid cycle, promoting the metabolism of sugars, fats, and amino acids, and participating in energy synthesis; NAD+is also the only substrate for coenzyme I consuming enzymes (the only substrate for DNA repair enzyme PARP, longevity protein Sirtuins, and cyclic ADP ribose synthase CD38/157).
NAD+is involved in all aspects of human metabolism and is a crucial coenzyme. Without NAD+, metabolism cannot function properly. Elderly people lack NAD+, which can lead to various problems, big and small. By supplementing with NAD+, comprehensive anti-aging can be achieved.
Pre clinical studies have shown that NMN has a variety of pharmacological activities in heart and brain ischemia, Alzheimer's disease, type 2 diabetes and obesity caused by diet and age. As a precursor of NAD+, NMN mainly synthesizes NAD+in vivo to play a pharmacological role, all of which are related to the lack of NAD+.

preparation
Add 150ml of phosphate buffer solution to a 500ml four necked bottle.
Add 2g of magnesium chloride, 10g of ATP, 7g of ribose, and 10g of nicotinamide at once, and stir at 35 ℃.
Measure the pH value of the reaction system and adjust it to pH 8.0 with a 10% Na2CO3 solution. Then add 1g of RK enzyme powder and 2g of NAMPT enzyme powder and stir to dissolve.
Stir the reaction at 37 ℃ and 200rpm, and monitor the conversion rate of the reaction using liquid chromatography-mass spectrometry. After 6 hours of reaction, detect that ATP has been consumed and stop the reaction. Through further filtration, HZ-818 macroporous resin adsorption, freeze-drying, ethanol and water recrystallization can obtain β - nicotinamide mononucleotide nicotinamide mononucleotide NMN with a yield of 70%.

biological activity
Nicotinamide mononucleoside (β - NM, NMN) is one of the key precursors of NAD+and a product of the NAMPT reaction, which is converted to NAD+by nicotinamide mononucleotide adenylate transferase.
Target point
Human Endogenous Metabolite

β-nicotinamidemononucleotidehasseveralbeneficialpharmacologicalactivities.MostlymediatedbyitsinvolvementinNAD+biosynthesis,thepharmacologicalactivitiesofNMNincludeitsroleincellularbiochemicalfunctions,cardioprotection,diabetes,Alzheimer'sdisease,andcomplicationsassociatedwithobesity.ChemicalbookTheintracellularNAD+levelsaresignificantlydecreasedbyknockdownorknockoutofNampt(NamptKDorNamptKO)ortreatmentwithNamptinhibitorFK866,whereasNAD+levelsaredramaticallyincreasedbysupplementofNAD+precursorsNAMorNMN(0.5–1mM).NAD+precursorNMNtreatmentinhibitedCD8+Tcellsactivationandfunction.
In vitro research

β-nicotinamide mononucleotide has several beneficial pharmacological activities. Mostly mediated by its involvement in NAD+ biosynthesis, the pharmacological activities of NMN include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer's disease, and complications associated with obesity. The intracellular NAD+ levels are significantly decreased by knockdown or knockout of Nampt (Nampt KD or Nampt KO) or treatment with Nampt inhibitor FK866, whereas NAD+ levels are dramatically increased by supplement of NAD+ precursors NAM or NMN (0.5–1 mM). NAD+ precursor NMN treatment inhibited CD8+ T cells activation and function. 体内研究 β-Nicotinamide mononucleotide (500 mg/kg; i.p.; 3 times per week for 7-10 week) prevents mtDNA damage and Dox-induced cardiac dysfunction. Nampt KO markedly inhibits tumor progression, whereas Nampt metabolite β-Nicotinamide mononucleotide (300 mg/kg body weight; i.p.; once every two days for 2 weeks) significantly promotes tumor growth in C57BL/6 mice (bearing wildtype Hepa1-6 cells). The reduction and increase in NAD+ level of respective Nampt KO and β-Nicotinamide mononucleotide-treated tumors are confirmed. β-nicotinamide mononucleotide ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. β-nicotinamide mononucleotide also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Animal Model: C57BL6 mice (p53 −/− mice) Dosage: 500 mg/kg Administration: I.p.; 3 times per week for 7-10 week Result: Prevented the significant decline in cardiac function of Dox-treated p53 −/− mice (study week 7 versus 10) along with rescuing the decreased mitochondrial respiration and tissue ATP depletion caused by Doxorubicin (Dox).