Cytidindiphosphatcholin | 99470-45-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: Cytidindiphosphatcholin
• 英文别名: Cytidine diphosphate choline；[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 99470-45-8
• 化学式: C₁₄H₂₅N₄O₁₁P₂
• 分子量: 487.32
• InChiKey: RZZPDXZPRHQOCG-OJAKKHQRSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  216
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1,2-dioleoylglycerol 、 Cytidindiphosphatcholin 生成 1,2-二油酰基-sn-甘油-3-磷酸胆碱 、 cytidine 5'-monophosphate 、 氢(+1)阳离子
  参考文献：
  名称：

  Hjelmstad R.H.; Bell R.M., J Biol Chem, 1991, 0021-9258, 4357-65

  摘要：

  DOI：
• 作为产物：
  描述：

  cytidine 5'-triphosphate 、 氢(+1)阳离子 、 phosphocholine 生成 Cytidindiphosphatcholin 、 pyrophosphoric acid
  参考文献：
  名称：

  哺乳动物 CTP 的晶体结构：磷酸胆碱胞苷酰转移酶催化结构域揭示了高度保守的核苷酸转移酶折叠内的新型活性位点残基。

  摘要：

  CTP：磷酸胆碱胞苷转移酶 (CCT) 是合成磷脂酰胆碱的关键调控酶，磷脂酰胆碱是真核细胞膜中含量最丰富的磷脂。CCT 催化的胞苷酰基团从 CTP 转移到磷酸胆碱以形成 CDP 胆碱是由其 C 端膜结合域赋予的膜脂依赖性机制调节的。我们首次分析了真核 CCT 的晶体结构。跨越残基 1-236 (CCT236) 的大鼠 CCTalpha 的删除构造缺乏调节域，因此显示组成性活动。2.2-A 结构揭示了与反应产物 CDP-胆碱复合的 CCT236 同源二聚体。每条链由一个完整的催化结构域组成，具有密切相关的 N 端延伸，它与催化域一起形成二聚体界面。尽管 CCT236 结构揭示了与胞苷酸转移酶超家族的其他成员保守的结合胞苷的元素，但它也具有非保守的活性位点残基 His-168 和 Tyr-173，它们与 CDP-胆碱的 β-磷酸发生关键相互作用. 诱变和动力学分析证实了它们在磷酸胆碱结合和催化

  DOI：

  10.1074/jbc.m109.053363

文献信息

• Molecular cloning and characterization of the gene encoding cholinephosphate cytidylyltransferase in Saccharomyces cerevisiae
  作者：Yuko TSUKAGOSHI、Jun-ichi NIKAWA、Satoshi YAMASHITA

  DOI：10.1111/j.1432-1033.1987.tb13635.x

  日期：1987.12

  The structural gene for cholinephosphate cytidylyltransferase (CCT) was isolated from a Saccharomyces cerevisiae genomic library by means of complementation in a mutant of the yeast defective in the enzyme. The cloned DNA restored both the growth and cholinephosphate cytidylyltransferase activity of the mutant. Whereas the enzyme of the mutant was thermolabile, the enzyme produced by the transformant was indistinguishable in heat stability from that produced by the wild type. Strains carrying a multicopy recombinant plasmid overproduced cholinephosphate cytidylyltransferase. The overproduction of the enzyme brought about an increase in the synthesis of CDPcholine in the transformant, but there was no increase in the overall rate of phosphatidylcholine synthesis. The cloned DNA was subcloned into a 2.5‐kb DNA fragment. The nucleotide sequence which contained CCT was determined by the dideoxy chain‐termination method. The sequence contained an open reading frame capable of encoding a protein of 424 amino acid residues with a calculated relative molecular mass of 49379.31. Northern blot analysis showed that this DNA segment is transcribed in yeast cells and the length of the transcript is consistent with the putative translation product. Hydropathy analysis according to Kyte and Doolittle indicated that the primary translation product contains extended hydrophilic stretches in its N‐ and C‐terminal regions. The primary translation product contains a region showing local sequence homology with nucleotidyl‐transfer enzymes such as DNA polymerase (Escherichia coli), CDPdiacylglycerol pyrophosphatase (E. coli), 3‐deoxy‐manno‐octulosonate cytidylyltransferase (E. coli) and DNA ligase (T4 phage), suggesting that these five enzymes are evolutionarily related. Statistically significant sequence homology was also noted between the human c‐fos gene product and the enzyme.

  通过互补法，从酿酒酵母（Saccharomyces cerevisiae）的基因组文库中分离出了胆碱磷酸胞苷转移酶（CCT）的结构基因。克隆的DNA恢复了突变体的生长和胆碱磷酸胞苷转移酶活性。突变体的酶热不稳定性，而转化体产生的酶在热稳定性上与野生型产生的酶无法区分。携带多拷贝重组质粒的菌株过量产生了胆碱磷酸胞苷转移酶。该酶的过量产生使转化体中CDP胆碱的合成增加，但整体磷脂酰胆碱的合成速率并未增加。克隆的DNA被亚克隆到一个2.5-kb的DNA片段中。包含CCT的核苷酸序列通过巢式链终止法确定。该序列包含一个开放阅读框，可编码一个由424个氨基酸残基组成的蛋白质，其计算出的相对分子质量为49379.31。Northern印迹分析显示，该DNA片段在酵母细胞中转录，且转录本的长度与推测的翻译产物一致。根据Kyte和Doolittle的疏水性分析，主要翻译产物在N端和C端区域具有扩展的疏水区域。主要翻译产物中有一个区域显示出与脱氧核核苷酸转移酶（如<;大肠杆菌;DNA聚合酶、CDP二酰基甘油焦磷酸水解酶、3-去氧-;曼诺;辛酮酸胞苷转移酶以及T4噬菌体DNA连接酶）的局部序列同源性，表明这五种酶在进化上相关。此外，人;c-fos;基因产物与该酶之间也存在统计学意义上的序列同源性。
• Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase: a novel metallophosphoesterase family preferentially expressed in rodent immune cells
  作者：José Canales、Ascensión Fernández、João Meireles Ribeiro、Alicia Cabezas、Joaquim Rui Rodrigues、José Carlos Cameselle、María Jesús Costas

  DOI：10.1042/bj20071471

  日期：2008.7.1

  ADPRibase-Mn (Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase) was earlier isolated from rat liver supernatants after separation from ADPRibase-I and ADPRibase-II (Mg2+-activated ADP-ribose pyrophosphatases devoid of CDP-alcohol pyrophosphatase activity). The last mentioned are putative Nudix hydrolases, whereas the molecular identity of ADPRibase-Mn is unknown. MALDI (matrix-assisted laser-desorption ionization) MS data from rat ADPRibase-Mn pointed to a hypothetical protein that was cloned and expressed and showed the expected specificity. It is encoded by the RGD1309906 rat gene, which so far has been annotated simply as ‘hydrolase’. ADPRibase-Mn is not a Nudix hydrolase, but it shows the sequence and structural features typical of the metallophosphoesterase superfamily. It may constitute a protein family of its own, the members of which appear to be specific to vertebrates, plants and algae. ADP-ribose was successfully docked to a model of rat ADPRibase-Mn, revealing its putative active centre. Microarray data from the GEO (Gene Expression Omnibus) database indicated that the mouse gene 2310004I24Rik, an orthologue of RGD1309906, is preferentially expressed in immune cells. This was confirmed by Northern-blot and activity assay of ADPRibase-Mn in rat tissues. A possible role of ADPRibase-Mn in immune cell signalling is suggested by the second-messenger role of ADP-ribose, which activates TRPM2 (transient receptor potential melastatin channel-2) ion channels as a mediator of oxidative/nitrosative stress, and by the signalling function assigned to many of the microarray profile neighbours of 2310004I24Rik. Furthermore, the influence of ADPRibase-Mn on the CDP-choline or CDP-ethanolamine pathways of phospholipid biosynthesis cannot be discounted.

  ADPRibase-Mn （Mn2+ 依赖性 ADP-ribose/CDP-alcohol 焦磷酸酶）是早些时候从大鼠肝脏上清液中分离出来的，分离后的 ADPRibase-I 和 ADPRibase-II（Mg2+ 激活的 ADP-ribose 焦磷酸酶，无 CDP-alcohol 焦磷酸酶活性）。最后提到的是推定的 Nudix 水解酶，而 ADPRibase-Mn 的分子特征尚不清楚。大鼠 ADPRibase-Mn 的 MALDI（基质辅助激光解吸电离）质谱数据表明，它是一种克隆和表达的假定蛋白，并显示出预期的特异性。它由 RGD1309906 大鼠基因编码，迄今为止该基因仅被注释为 "水解酶"。ADPRibase-Mn 不是一种 Nudix 水解酶，但它显示出金属磷酸酯酶超家族的典型序列和结构特征。它可能自成一个蛋白家族，其成员似乎是脊椎动物、植物和藻类特有的。ADP-ribose 与大鼠 ADPRibase-Mn 的模型对接成功，揭示了其推定的活性中心。来自 GEO（基因表达总库）数据库的微阵列数据表明，RGD1309906 的同源基因小鼠基因 2310004I24Rik 优先在免疫细胞中表达。大鼠组织中的 Northern-blot 和 ADPRibase-Mn 活性测定证实了这一点。ADP-ribose 可激活 TRPM2（瞬时受体电位美司他丁通道-2）离子通道，成为氧化/亚硝基应激的介质，而 2310004I24Rik 的许多微阵列图谱邻域都具有信号功能，这表明 ADPRibase-Mn 可能在免疫细胞信号中发挥作用。此外，还不能排除 ADPRibase-Mn 对磷脂生物合成的 CDP-choline 或 CDP-ethanolamine 途径的影响。
• Rat liver nucleoside diphosphosugar or diphosphoalcohol pyrophosphatases different from nucleotide pyrophosphatase or phosphodiesterase I: substrate specificities of Mg2+- and/or Mn2+-dependent hydrolases acting on ADP-ribose
  作者：José Canales、Rosa María Pinto、María Jesús Costas、María Teresa Hernández、Asunción Miró、Diego Bernet、Ascensión Fernández、JoséCarlos Cameselle

  DOI：10.1016/0167-4838(94)00191-i

  日期：1995.1

  Three rat liver nucleotides(5') diphosphosugar (NDP-sugar) or nucleoside(5') diphosphoalcohol pyrophosphatases are described: two were previously identified in experiments measuring Mg(2+)-dependent ADP-ribose pyrophosphatase activity (Miró et al. (1989) FEBS Lett. 244, 123-126), and the other is a new, Mn(2+)-dependent ADP-ribose pyrophosphatase. They are resolved by ion-exchange chromatography, and

  描述了三种大鼠肝脏核苷酸（5'）二磷酸糖（NDP-糖）或核苷（5'）二磷酸醇焦磷酸酶：先前在测量Mg（2+）依赖的ADP-核糖焦磷酸酶活性的实验中确定了两种（Miró等人（ 1989）FEBS Lett.244，123-126），另一个是新的依赖于Mn（2+）的ADP-核糖焦磷酸酶。它们通过离子交换色谱分离，并且在底物和阳离子特异性，ADP核糖的KM值，pH活性曲线，分子量和等电点方面有所不同。测试了这些酶的活性：还原性（ADP-核糖，IDP-核糖）和非还原性NDP-糖（ADP-葡萄糖，ADP-甘露糖，GDP-甘露糖，UDP-甘露糖，UDP-葡萄糖，UDP-木糖， CDP-葡萄糖），CDP-醇（CDP-甘油，CDP-乙醇胺，CDP-胆碱），二核苷酸（焦磷酸二腺苷，NADH，NAD +，FAD），单和二磷酸核苷（5'）（AMP，CMP，GMP，ADP，CDP）和dTMP对硝基苯酯。由于未将酶
• Biosynthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor and a hypotensive lipid) by cholinephosphotransferase in various rat tissues
  作者：Willem Renooij、Fred Snyder

  DOI：10.1016/0005-2760(81)90182-x

  日期：1981.2

  the present study, microsomal preparations from several rat tissues were found to catalyze the synthesis of 1-alkyl-1-acetyl-sn-glycero-3-phosphocholine by 1-alkyl-2-acetyl-sn-glycerol:CDPcholine cholinephosphotransferase reaction. Optimal conditions to measure enzyme activity were established. A subcellular survey of this cholinephosphotransferase activity showed that the enzyme was of microsomal origin

  据报道，独特的烷基磷脂1-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱具有强大的降压活性（Blank，ML，Snyder，F.，Byers，LW，Brooks，B.和Muirhead， EE（1979）Biochem。Biophys。Res。Commun。90，1194-1200），并且似乎是非常有效的血小板活化因子（Demopoulos，CA，Pinckard，RN和Hanahan，DJ（1979）J. Biol。Chem。 254，9355-9358）。在本研究中，发现来自几个大鼠组织的微粒体制剂通过1-烷基-2-乙酰基-sn-甘油：CDP胆碱胆碱磷酸转移酶反应催化1-烷基-1-乙酰基-sn-甘油-3-磷酸胆碱的合成。建立了测定酶活性的最佳条件。对该胆碱磷酸转移酶活性的亚细胞调查显示该酶是微粒体来源的。在几个组织的微粒体中发现了酶的活性。但是，脾脏在被检查的组织中具有最高的活性。发现三种
• Choline glycerophospholipid biosynthesis in the guinea pig heart
  作者：Monika Wientzek、Ricky Y. K. Man、Patrick C. Choy

  DOI：10.1139/o87-112

  日期：1987.10.1

  The aims of this study were to (i) elucidate the biosynthetic pathways for the formation of plasmenylcholine in the mammalian heart and (ii) investigate whether the control of choline glycerophospholipid production is different in hearts with high plasmenylcholine content. Guinea pig hearts were used throughout this study, since 34% of the cardiac choline glycerophospholipids in this species is present in the plasmenylcholine form. By perfusion of the guinea pig heart in the Langendorff mode with labeled choline, we demonstrated that the majority of plasmenylcholine in the heart was synthesized via the CDP-choline pathway. The ability of the heart to form plasmenylcholine from CDP-choline and 1-alkenyl-2-acylglycerol was also shown. We postulate that 1-alkenyl-2-acylglycerol in the guinea pig heart might originate from the hydrolysis of plasmenylethanolamine. In mammalian liver and other tissues, the CDP-choline pathway is the major pathway for phosphatidylcholine biosynthesis and the rate-limiting step is catalyzed by CTP:phosphocholine cytidylyltransferase. The results obtained from the present study support this supposition. In addition, evidence was obtained indicating that phosphorylation of choline by choline kinase in the CDP-choline pathway may also be rate limiting. Although the involvement of choline kinase as a rate-limiting enzyme in the CDP-choline pathway has been shown in a number of cell cultures, the rate-limiting role of this enzyme in intact mammalian organs has not been previously reported. The rationale for the presence of more than one rate-limiting step in the CDP-choline pathway in the guinea pig heart remains undefined.

  本研究的目的是(i) 阐明哺乳动物心脏中形成磷脂酰胆碱的生物合成途径，以及(ii) 探讨高磷脂酰胆碱含量的心脏是否有不同的胆碱甘油磷脂产生控制。本研究使用豚鼠心脏，因为该物种心脏中34％的胆碱甘油磷脂以磷脂酰胆碱形式存在。通过使用标记的胆碱对豚鼠心脏进行Langendorff灌流，我们证明了心脏中大部分的磷脂酰胆碱是通过CDP-胆碱途径合成的。还展示了心脏从CDP-胆碱和1-烯基-2-酰基甘油形成磷脂酰胆碱的能力。我们推测，豚鼠心脏中的1-烯基-2-酰基甘油可能来自于磷脂酰乙醇胺的水解。在哺乳动物肝脏和其他组织中，CDP-胆碱途径是磷脂酰胆碱生物合成的主要途径，速率限制步骤由CTP：磷酸胆碱胞苷酸转移酶催化。本研究获得的结果支持这一假设。此外，还获得了证据表明，CDP-胆碱途径中的胆碱经胆碱激酶磷酸化也可能是速率限制步骤。尽管在许多细胞培养中已经显示了胆碱激酶作为CDP-胆碱途径中的速率限制酶的参与，但这种酶在完整的哺乳动物器官中的速率限制作用以前尚未报道。豚鼠心脏中CDP-胆碱途径存在多个速率限制步骤的原因尚未定义。