β-ニコチンアミドモノヌクレオチド

解説nicotinamide ribonucleotide．C11H15N2O8P(334.24)．略称NMN．老化現象の抑制に関わるとされるサーチュイン遺伝子を活性化する物質の一。ニコチン酸（ナイアシン）の一種で、もともと体内に存在するが加齢に伴って減少する。ニコチンアミドモノヌクレオチドは，NADの加水分解によって得られるが，化学的にも合成できる．無色の吸湿性粉末．水に易溶，アセトンに不溶．[α]20D－24°(水)．λmax 266 nm(ε 4600，pH 7.0)．pKa 3.9．酸化還元反応の補酵素活性はない．NAD，NADPの合成原料に用いられる．森北出版「化学辞典（第2版）

説明Nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. NMN is used for studying binding motifs within RNA aptamers and ribozyme activation processes involving β-nicotinamide mononucleotide (β-NMN)-activated RNA fragments.β-Nicotinamide mononucleotide (β-NMN) is an intermediate in the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed biosynthesis of nicotinamide adenine dinucleotide (NAD+). NAMPT mediates the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to produce β-NMN. β-NMN adenyltransferase subsequently converts β-NMN to NAD+.

使用β-Nicotinamide mononucleotide (NMN) is used to study binding motifs within RNA aptamers and ribozyme activation processes involving β-nicotinamide mononucleotide (β-NMN)-activated RNA fragments. NMN is a nucleotide derived from ribose and nicotinamide. Niacinamide (nicotinamide,) is a derivative of vitamin B3, also known as niacin.) As a biochemical precursor of NAD+, it may be useful in the prevention of pellagra.β-Nicotinamide mononucleotide is an intermediate in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to generate β-NMN, which is subsequently converted to NAD+ by β-NMN adenyltransferase.At 50-100 μM, β-NMN has been used to enhance NAD biosynthesis and glucose-stimulated insulin secretion in a Nampt+/- mouse model of metabolic disease, demonstrating a role for Nampt in β cell function.Furthermore, at 500 mg/kg/day, it has been shown to ameliorate glucose intolerance in high-fat diet-induced type 2 diabetes mice by restoring NAD+ levels.

一般的な説明β-Nicotinamide mononucleotide (β-NMN) is an intermediate in the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed biosynthesis of nicotinamide adenine dinucleotide (NAD+). NAMPT mediates the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to produce β-NMN. β-NMN adenyltransferase subsequently converts β-NMN to NAD+.

製造方法β-Nicotinamide mononucleotide is a NAD+intermediate. In recent years, the relation of NAD+metabolism and aging-associated disease is attracting attention from various research fields. Synthesis of β-nicotinamide mononucleotide (NMN) A solution of NAD (3.5 g, 5.28 mmol) and ZrCl4(6.15 g, 26.4 mmol) in 500 ml water was stirred at 50°C for 30 min. The hydrolysis was monitored by TLC (SiO2EtOH/ 1 M NH4Ac [7 : 3]). The reaction was quenched with 245mL of a 0.5 M solution of Na3PO4. After adjusting to pH 7 with a 2 M solution of HCl, a white precipitate was formed. The suspension was centrifuged 8 min,1,000rpm, the supernatant was collected and the pellet was washed two times with 200 mL water. The combined supernatants wereconcentrated to 1/3 of its volume on a rotary evaporator. The remaining solution was purified with a column filled with Dowex 50WX8 (100-200 mesh, H+-Form, column-material: 2.5 x 30 cm). The column was loaded with 1.5 L5 % HCl and equilibrated with1.5L millipore water until pH 5 was reached. 100 mL of the concentrated solution was loaded on the ion exchange column and eluted with Milliporewater. The first cleavage product eluted was NMN (615 mg, 1.84 mmol,yield:35 %) and yielded a colorless solid after evaporation of the solvent, followed by AMP. 1H NMR (500MHz, D2O)δ: 9.48 (s, 1 H), 9.31 (d,J= 6.2 Hz, 1 H), 9.00 (d,J= 8.2 Hz, 1 H), 8.32 (dd,J= 8.2, 6.2 Hz, 1 H), 6.24 (d,J=5.4 Hz, 1 H), 4.68-4.64 (m, 1 H), 4.58 (t, 1 H), 4.48-4.45 (m, 1 H), 4.36–4.14 (m,J= 12.0, 2 H). 13C NMR (75 MHz, d2o) δ: 165.50, 145.65, 142.15, 139.53, 133.62, 128.19, 99.65, 87.18, 87.06, 77.42, 70.71, 63.89, 63.82. 31P NMR (202 MHz, D2O)δ:-0.03

純化方法Purify NMN by passage through a column of Dowex-1 (Clform) and washing with H2O until no absorbance is observed at 260 nm. The tubes containing NMN are pooled, adjusted to pH 5.5-6 and evaporated in vacuo to a small volume. This is adjusted to pH 3 with dilute HNO3 in an ice-bath and treated with 20volumes of Me2CO at 0-5o. The heavy white precipitate is collected by centrifugation at 0o. It is best stored wet and frozen or it can be dried to give a gummy residue. It has max 266nm ( 4,600) and min 249nm ( 3600) at pH 7.0 (i.e. no absorption at 340nm). It can be estimated by reaction with CNor hydrosulfite which form the 4-adducts (equivalent to NADH) which have UV max 340nm ( 6,200). Thus after reaction, an OD340 of one is obtained from a 0.1612mM solution in a 1cm path cuvette. [Plaut & Plaut Biochemical Preparations 5 56 1957, Maplan & Stolzenbach Methods Enzymol 3 899 1957, Kaplan et al. J Am Chem Soc 77 815 1955, Beilstein 22/2 V 168.]

定義本品は、次の化学式で表される有機化合物である。

定義ChEBI: β-Nicotinamide Mononucleotide is a condensation product of nicotinamide and ribose 5-phosphate, in which the nitrogen of nicotinamide is linked to the (β) c-l of the ribose. NMN zwitterion is a nicotinamide mononucleotide. It has a role as an Escherichia coli metabolite and a mouse metabolite. It is a conjugate base of a NMN(+). It is a conjugate acid of a NMN(-).