ナダイド

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)．

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.

来歴β-Nicotinamide adenine dinucleotide 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+.

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.

純化方法β-Nicotinamide adenine dinucleotide 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.]

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 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)