a b Hwang SJ, Durnin L, Dwyer L, Rhee PL, Ward SM, Koh SD, Sanders KM, Mutafova-Yambolieva VN (2011). "β-nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons". Gastroenterology. 140 (2): 608–617.e6. doi: 10.1053/j.gastro.2010.09.039. PMC 3031738. PMID 20875415. Levine OS, Schuchat A, Schwartz B, Wenger JD, Elliott J (1997). "Generic protocol for population-based surveillance of Haemophilus influenzae type B" (PDF). World Health Organization. Centers for Disease Control. p. 13. WHO/VRD/GEN/95.05. Archived from the original (PDF) on 1 July 2004. Todisco S, Agrimi G, Castegna A, Palmieri F (2006). "Identification of the mitochondrial NAD + transporter in Saccharomyces cerevisiae". J. Biol. Chem. 281 (3): 1524–31. doi: 10.1074/jbc.M510425200. PMID 16291748. Goto M, Muramatsu H, Mihara H, Kurihara T, Esaki N, Omi R, Miyahara I, Hirotsu K (2005). "Crystal structures of Delta1-piperideine-2-carboxylate/Delta1-pyrroline-2-carboxylate reductase belonging to a new family of NAD(P)H-dependent oxidoreductases: conformational change, substrate recognition, and stereochemistry of the reaction". J. Biol. Chem. 280 (49): 40875–84. doi: 10.1074/jbc.M507399200. PMID 16192274. Senkovich O, Speed H, Grigorian A, et al. (2005). "Crystallization of three key glycolytic enzymes of the opportunistic pathogen Cryptosporidium parvum". Biochim. Biophys. Acta. 1750 (2): 166–72. doi: 10.1016/j.bbapap.2005.04.009. PMID 15953771.

Besides assembling NAD + de novo from simple amino acid precursors, cells also salvage preformed compounds containing a pyridine base. The three vitamin precursors used in these salvage metabolic pathways are nicotinic acid (NA), nicotinamide (Nam) and nicotinamide riboside (NR). [6] These compounds can be taken up from the diet and are termed vitamin B 3 or niacin. However, these compounds are also produced within cells and by digestion of cellular NAD +. Some of the enzymes involved in these salvage pathways appear to be concentrated in the cell nucleus, which may compensate for the high level of reactions that consume NAD + in this organelle. [40] There are some reports that mammalian cells can take up extracellular NAD + from their surroundings, [41] and both nicotinamide and nicotinamide riboside can be absorbed from the gut. [42] Yoshino M, et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. It has been studied for its potential use in the therapy of neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as multiple sclerosis. [6] [80] [96] [77] A placebo-controlled clinical trial of NADH (which excluded NADH precursors) in people with Parkinson's failed to show any effect. [97]Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature. 425 (6954): 191–196. Bibcode: 2003Natur.425..191H. doi: 10.1038/nature01960. PMID 12939617. S2CID 4395572. The coenzyme NAD + is also consumed in ADP-ribose transfer reactions. For example, enzymes called ADP-ribosyltransferases add the ADP-ribose moiety of this molecule to proteins, in a posttranslational modification called ADP-ribosylation. [66] ADP-ribosylation involves either the addition of a single ADP-ribose moiety, in mono-ADP-ribosylation, or the transferral of ADP-ribose to proteins in long branched chains, which is called poly(ADP-ribosyl)ation. [67] Mono-ADP-ribosylation was first identified as the mechanism of a group of bacterial toxins, notably cholera toxin, but it is also involved in normal cell signaling. [68] [69] Poly(ADP-ribosyl)ation is carried out by the poly(ADP-ribose) polymerases. [67] [70] The poly(ADP-ribose) structure is involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance. [70] In addition to these functions within the cell, a group of extracellular ADP-ribosyltransferases has recently been discovered, but their functions remain obscure. [71]

a b c Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M, Zocchi E (2006). "Emerging functions of extracellular pyridine nucleotides". Mol. Med. 12 (11–12): 324–7. doi: 10.2119/2006-00075.Billington. PMC 1829198. PMID 17380199. Li et al. have found that NAD + directly regulates protein-protein interactions. [83] They also show that one of the causes of age-related decline in DNA repair may be increased binding of the protein DBC1 (Deleted in Breast Cancer 1) to PARP1 (poly[ADP–ribose] polymerase 1) as NAD + levels decline during aging. [83] Thus, the modulation of NAD + may protect against cancer, radiation, and aging. [83] Extracellular actions of NAD + edit Nelson DL; Cox MM (2004). Lehninger Principles of Biochemistry (4th ed.). W. H. Freeman. ISBN 978-0-7167-4339-2. a b Mutafova-Yambolieva VN, Hwang SJ, Hao X, Chen H, Zhu MX, Wood JD, Ward SM, Sanders KM (2007). "Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle". Proc. Natl. Acad. Sci. U.S.A. 104 (41): 16359–64. Bibcode: 2007PNAS..10416359M. doi: 10.1073/pnas.0705510104. PMC 2042211. PMID 17913880. In cellular metabolism, NAD is involved in redox reactions, carrying electrons from one reaction to another, so it is found in two forms: NAD + is an oxidizing agent, accepting electrons from other molecules and becoming reduced; with H +, this reaction forms NADH, which can be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD. It is also used in other cellular processes, most notably as a substrate of enzymes in adding or removing chemical groups to or from proteins, in posttranslational modifications. Because of the importance of these functions, the enzymes involved in NAD metabolism are targets for drug discovery.Most organisms synthesize NAD + from simple components. [6] The specific set of reactions differs among organisms, but a common feature is the generation of quinolinic acid (QA) from an amino acid – either tryptophan (Trp) in animals and some bacteria, or aspartic acid (Asp) in some bacteria and plants. [32] [33] The quinolinic acid is converted to nicotinic acid mononucleotide (NaMN) by transfer of a phosphoribose moiety. An adenylate moiety is then transferred to form nicotinic acid adenine dinucleotide (NaAD). Finally, the nicotinic acid moiety in NaAD is amidated to a nicotinamide (Nam) moiety, forming nicotinamide adenine dinucleotide. [6] Mendelsohn AR, et al. (2014). Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels.

Timmins GS, Deretic V (2006). "Mechanisms of action of isoniazid". Mol. Microbiol. 62 (5): 1220–1227. doi: 10.1111/j.1365-2958.2006.05467.x. PMID 17074073. S2CID 43379861. Based on studies, Tru Niagen’s nicotinamide riboside (NR) assists cellular energy production as well as cellular repair. A daily dose of Tru Niagen increases NAD+ by 80%, reducing aging and promoting cellular energy production and overall health and well-being. Guse AH (2004). "Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR)". Curr. Mol. Med. 4 (3): 239–48. doi: 10.2174/1566524043360771. PMID 15101682. So far, there are no reported adverse side effects of taking NAD+ supplements. But the safety of long-term use and high-dose supplementation is still under study. “NAD+ IV therapy is usually done very slowly to minimise a sensation of muscle cramping or nausea – that tends to pass in about 10 minutes,” says Angelova. Think of NAD supplements as a top-up to your natural supply. They are designed to help boost the amount of NAD circulating in your bloodstream. The benefits of NAD supplementsThere are many different superfamilies of enzymes that bind NAD + / NADH. One of the most common superfamilies includes a structural motif known as the Rossmann fold. [52] [53] The motif is named after Michael Rossmann, who was the first scientist to notice how common this structure is within nucleotide-binding proteins. [54] Warburg O, Christian W (1936). "Pyridin, der wasserstoffübertragende bestandteil von gärungsfermenten (pyridin-nucleotide)" [Pyridin, the hydrogen-transferring component of the fermentation enzymes (pyridine nucleotide)]. Biochemische Zeitschrift (in German). 287: 291. doi: 10.1002/hlca.193601901199.

Note that two of the authors involved in this study are listed as inventors on patents involving the use of NMN. Rao ST, Rossmann MG (1973). "Comparison of super-secondary structures in proteins". J Mol Biol. 76 (2): 241–56. doi: 10.1016/0022-2836(73)90388-4. PMID 4737475. Hair and nail growth: Some supplement users have seen an improvement in the health of their hair and nails. “This is because when your cellular health improves, the body invests more resources into these less important areas of our biology,” explains Conlon. Science.bio NR Chloride Powder offers the highest doses of nicotinamide riboside. The jar can withstand UV rays, preventing deterioration of the supplement.

Imai S (2016). "The NAD World 2.0: the importance of the inter-tissue communication mediated by NAMPT/NAD +/SIRT1 in mammalian aging and longevity control". npj Systems Biology and Applications. 2: 16018. doi: 10.1038/npjsba.2016.18. PMC 5516857. PMID 28725474. Because cancer cells utilize increased glycolysis, and because NAD enhances glycolysis, nicotinamide phosphoribosyltransferase (NAD salvage pathway) is often amplified in cancer cells. [94] [95]