Nicotinamide mononucleotide: Difference between revisions

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'''Nicotinamide mononucleotide''' ("'''NMN'''" and "'''β-NMN'''") is a [[nucleotide]] derived from [[ribose]], [[nicotinamide]], [[nicotinamide riboside]] and [[Niacin (substance)|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 ([[Nicotinamide adenine dinucleotide|NAD+]]) through the [[SLC12A8|Slc12a8]] transporter. and the matter remains unsettled.

Because NADH is a [[Cofactor (biochemistry)|cofactor]] for processes inside [[mitochondria]], for [[sirtuin]]s and [[Poly (ADP-ribose) polymerase|PARP]], NMN has been studied in [[animal model]]s 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 [[Hard sell|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 testing|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]].

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 of nicotinamide mononucleotide has been redacted since the latter half of 2022 by the [[Food and Drug Administration|FDA]] because it is under investigation as a pharmaceutical drug.

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.

NMN is a precursor for [[Nicotinamide adenine dinucleotide|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 (naturally occurring)|DNA damage]], [[Neurodegenerative disease|neurodegeneration]] and [[inflammation|inflammatory responses]]. Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Adv Nutr. 2023 Nov;14(6):1416-1435. doi: 10.1016/j.advnut.2023.08.008. Epub 2023 Aug 22. PMID: 37619764; PMCID: PMC10721522</ref> The potential benefits and risks of NMN supplementation, as of 2023, are currently under investigation.

Certain enzymes are sensitive to the intracellular NMN/[[Nicotinamide adenine dinucleotide|NAD⁺]] ratio, such as [[SARM1]], a protein responsible for initiating cellular degeneration pathways such as [[MAP kinase]] and inducing [[axon|axonal]] loss and [[necrosis|neuronal death]]. [[NMNAT1|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.

{{二次利用|date=5 April 2024}}

[[Category:Nucleotides]]