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外観

白色～ほとんど白色粉末～結晶

定義

本品は、次の化学式で表される有機化合物である。

解説

ニコチンアミドアデニンジヌクレオチド略称NAD．以前は補酵素Ⅰ(CoⅠ)，あるいはDPN(ジホスホピリジンヌクレオチド)ともよばれた．下の表に示したような酸化還元酵素の補酵素で，構造式は次のとおりである．NAD＋は還元型基質から水素を受けとりそれを酸化し，還元型NAD(NADH)と H＋ を生成する．NAD＋の還元は次に示すようにニコチン酸アミドの部位で起こる．この反応は可逆的である．吸湿性の白色の粉末．水に易溶．酵母から単離されるが，ニコチンアミドモノヌクレオチドとアデノシン5′-リン酸との脱水縮合で合成される．NAD＋：[α]_D －31.5°(水)．λmax 259 nm(ε 17.6×106)．NADH：[α]_D ＋14.8°(水)．λmax 340 nm(ε 6.2×106)．NAD＋が関与するアルコール脱水素酵素の反応は次のように示される．　　

CH3CH2OH ＋ NAD＋⇄ CH3CHO ＋ NADH ＋ H＋　　

反応が右へ進行するとき340 nm の吸光度は増加する．これを利用して酵素反応速度を測定することができる．また，NADHはフラビンを介してグルタチオンやシトクロムを還元する作用がある．　　

NADH ＋ H＋ ＋ FAD → NAD＋ ＋ FADH2　　

FADH2 ＋ 酸化型グルタチオン → FAD ＋ 2還元型グルタチオン　　

また，NAD＋はDNAが切断されたとき，それを修復する酵素DNAリガーゼの作用にも関与する．LD50 4.333 g/kg(マウス，腹腔)．

化粧品の成分用途

皮膚コンディショニング剤

効能

補酵素

説明

β-Nicotinamide adenine dinucleotide (NAD+) plays a major role in metabolism as a cofactor and mobile electron acceptor. NAD+ is a required oxidizing cosubstrate for many enzymes. It is reduced to NADH (Cat# N-035) which carries electrons to the electron transport chain for subsequent oxidative phorphorylation and ATP production. NAD+ is capable of donating ADP-ribose moieties to a protein, producing nicotinamide in the process. Sirtuin enzymes use NAD+ as a substrate to deacetylate proteins and direct activity between the nucleus and mitochondria. NAD+ is regenerated by fermentation and by oxidative phosphorylation.

化学的特性

Beta-Nicotinamide adenine dinucleotide is a hygroscopic white powder. It should be stored desiccated. Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature -20°C.

来歴

The coenzyme NAD⁺ was first discovered by British biochemists Arthur Harden and William John Young in 1906. They observed that the addition of boiled and filtered yeast extract significantly increased the rate of alcoholic fermentation in unboiled yeast extracts. They named the unidentified factor responsible for this effect a coferment. By extensively purifying it from yeast extracts, Hans von Euler-Chelpin identified this heat-stable factor as a nucleotide sugar phosphate. In 1936, German scientist Otto Heinrich Warburg demonstrated the role of this nucleotide coenzyme in hydride transfer and determined the nicotinamide portion as the site of redox reactions. Vitamin precursors of NAD+ were first identified in 1938, when Conrad Elvehjem showed that liver has an "anti-black tongue" activity in the form of nicotinamide. Then, in 1939, he provided the first strong evidence that niacin is used to synthesize NAD⁺.

主な応用

β-Nicotinamide adenine dinucleotide (β-NAD) is a cofactor of alcohol dehydrogenase and acts as a neuromodulator and an inhibitory neurotransmitter in visceral smooth muscles. The NAD/NADH ratio has a role in the regulation of intracellular redox potential. It thereby influences metabolic reactions in vivo. It has been used for the preparation of deacetylated tubulin. It has also been used for UDP-glucose-6-hydrogenase (UGDH) enzyme activity assay of orital fibroblast cell lysates.
β-Nicotinamide adenine dinucleotide (NAD+) and β-Nicotinamide adenine dinucleotide, reduced (NADH) comprise a coenzyme redox pair (NAD+:NADH) involved in a wide range of enzyme catalyzed oxidation reduction reactions. In addition to its redox function, NAD+/NADH is a donor of ADP-ribose units in ADP-ribosylaton (ADP-ribosyltransferases; poly(ADP-ribose) polymerases ) reactions and a precursor of cyclic ADP-ribose (ADP-ribosyl cyclases).

定義

ChEBI: β-Nicotinamide adenine dinucleotide (NAD) is the oxidized form of β-Nicotinamide Adenine Dinucleotide. It exists as an anion under normal physio-logic conditions. It is functionally related to a deamido-NAD zwitterion. It is a conjugate base of a NAD(+). It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)

一般的な説明

β-Nicotinamide adenine dinucleotide (NAD) is a ubiquitously found electron carrier and a cofactor. NAD⁺ contains an adenylic acid and a nicotinamide-5′-ribonucleotide group linked together by a pyrophosphate moiety. In NAD⁺ complexes, the enzyme-cofactor interactions are highly conserved.

生物活性

NAD+, known more formally as nicotinamide adenine dinucleotide, is a signaling molecule as well as a cofactor or substrate for many enzymes. It acts as an oxidizing agent, accepting electrons from other molecules while being converted to its reduced form, NADH. NAD+ is also essential for the activity of several enzymes, including poly(ADP)-ribose polymerases and cADP-ribose synthases. For example, it is used by some sirtuins to mediate protein deacetylation, producing O-acetyl-ADP-ribose and nicotinamide as well as the deacetylated protein.

副作用

In the studies conducted thus far, people taking between 1000mg-2000mg per day have reported zero long term side effects. However, during the active infusion, some people may feel temporary nausea or stomach discomfort.

純化方法

NAD is purified by paper chromatography or better on a Dowex-1 ion-exchange resin. The column is prepared by washing with 3M HCl until free of material absorbing at 260nm, then with water, 2M sodium formate until free of chloride ions and, finally, with water. NAD, as a 0.2% solution in water, is adjusted with NaOH to pH 8, and adsorbed onto the column, washed with water, and eluted with 0.1M formic acid. Fractions with strong absorption at 360nm are combined, acidified to pH 2.0 with 2M HCl, and cold acetone (ca 5L/g of NAD) is added slowly and with constant agitation. It is left overnight in the cold, then the precipitate is collected in a centrifuge, washed with pure acetone and dried under vacuum over CaCl2 and paraffin wax shavings [Kornberg Methods Enzymol 3 876 1957]. It has been purified by anion-exchange chromatography [Dalziel & Dickinson Biochemical Preparations 11 84 1966.] The purity is checked by reduction to NADH (with EtOH and yeast alcohol dehydrogenase) which has 340mn 6220 M-1cm-1. [Todd et al. J Chem Soc 3727, 3733 1957.] [pKa, Lamborg et al. J Biol Chem 231 685 1958.] The free acid crystallises from aqueous Me2CO with 3H2O and has m 140-142o. It is stable in cold neutral aqueous solutions in a desiccator (CaCl2) at 25o, but decomposes at strong acid and alkaline pH. Its purity is checked by reduction with yeast alcohol dehydrogenase and EtOH to NADH and noting the OD at 340nm. Pure NADH (see below) has 340 6.2 x 104 M-1cm-1, i.e. 0.1mole of NADH in 3mL and in a 1cm path length cell has an OD at 340nm of 0.207. [Beilstein 26 IV 3644.]

参考文献

1. Pollak N.; D?lle C.; Ziegler M. The power to reduce: pyridine nucleotides - small molecules with a multitude of functions. Biochem. J. 2007, 402(2), 205-18. DOI:10.1042/BJ20061638
2. Unden G, Bongaerts J. Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors. Biochim. Biophys. Acta. 1997, 1320(3), 217-34. DOI:10.1016/S0005-2728(97)00034-0
3. Houtkooper, R.H., Cantó, C., Wanders, R.J., et al. The secret life of NAD+: An old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 31(2), 194-223 (2010). DOI:10.1210/er.2009-0026
4. Experimental and theoretical electron density studies in large molecules: NAD+, beta-nicotinamide adenine dinucleotide DOI:10.1021/JP034478B
5. A Mechanism of Adsorption of beta-Nicotinamide Adenine Dinucleotide on Graphene Sheets: Experiment and Theory DOI:10.1002/chem.200900399
6. β-Nicotinamide Adenine Dinucleotide (β-NAD) Inhibits ATP-Dependent IL-1β Release from Human Monocytic Cells DOI:10.3390/ijms19041126
7. Oxidation of β-Nicotinamide Adenine Dinucleotide (NADH) by Au Cluster and Nanoparticle Catalysts Aiming for Coenzyme Regeneration in Enzymatic Glucose Oxidation DOI:10.1021/acssuschemeng.0c01893