6-phosphogluconate | 58000-20-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-phosphogluconate
• 英文别名: 6-phosphonatooxy-D-gluconate；(2R,3S,4R,5R)-2,3,4,5-tetrahydroxy-6-phosphonatooxyhexanoate
• CAS: 58000-20-7
• 化学式: C₆H₁₀O₁₀P
• 分子量: 273.113
• InChiKey: BIRSGZKFKXLSJQ-SQOUGZDYSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  194
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-phosphogluconate 在 乙二胺四乙酸 、 Proteus mirabilis 、 四环素 、 anthraquinone-2,6-disulfonate 、 二甲基亚砜 作用下， 以 水 为溶剂， 以98%的产率得到6-Phospho-D-arabino-hex-2-ulosonat
  参考文献：
  名称：

  Schinschel, Carsten; Simon, Helmut, Angewandte Chemie, 1993, vol. 105, # 8, p. 1221 - 1223

  摘要：

  DOI：
• 作为产物：
  描述：

  6-O-phosphonato-D-glucono-1,5-lactone(2-) 、 水 生成 6-phosphogluconate 、 氢(+1)阳离子
  参考文献：
  名称：

  NMR Spectroscopic Analysis of the First Two Steps of the Pentose-Phosphate Pathway Elucidates the Role of 6-Phosphogluconolactonase

  摘要：

  The pentose-phosphate pathway provides reductive power and nucleotide precursors to the cell through oxidative and nonoxidative branches, respectively. 6-Phosphogluconolactonase is the second enzyme of the oxidative branch and catalyzes the hydrolysis of 6-phosphogluconolactones, the products of glucose 6-phosphate oxidation by glucose-6-phosphate dehydrogenase. The role of 6-phosphogluconolactonase was still questionable, because 6-phosphogluconolactones were believed to undergo rapid spontaneous hydrolysis. In this work, nuclear magnetic resonance spectroscopy was used to characterize the chemical scheme and kinetic features of the oxidative branch. We show that 6-phosphogluconolactones have in fact a nonnegligible life. time and are highly electrophilic compounds. The delta form (1-5) of the lactone is the only product of glucose 6-phosphate oxidation. Subsequently, it leads to the gamma form (1-4) by intramolecular rearrangement. However, only the delta form undergoes spontaneous hydrolysis, they form being a "dead end" of this branch. The delta form is the only substrate for 6-phosphogluconolactonase. Therefore, 6-phosphogluconolactonase activity accelerates hydrolysis of the delta form, thus preventing its conversion into the gamma form. Furthermore, 6-phosphogluconolactonase guards against the accumulation of 5-6-phosphogluconolactone, which may be toxic through its reaction with endogenous cellular nucleophiles. Finally, the difference between activity of human, Trypanosoma brucei, and Plasmodium falciparum 6-phosphogluconolactonases is reported and discussed.

  DOI：

  10.1074/jbc.m105174200

文献信息

• Simultaneous Quantification of Metabolites Involved in Central Carbon and Energy Metabolism Using Reversed-Phase Liquid Chromatography−Mass Spectrometry and in Vitro ¹³C Labeling
  作者：Wen-Chu Yang、Miroslav Sedlak、Fred E. Regnier、Nathan Mosier、Nancy Ho、Jiri Adamec

  DOI：10.1021/ac801693c

  日期：2008.12.15

  Comprehensive analysis of intracellular metabolites is a critical component of elucidating cellular processes. Although the resolution and flexibility of reversed-phase liquid chromatography−mass spectrometry (RPLC−MS) makes it one of the most powerful analytical tools for metabolite analysis, the structural diversity of even the simplest metabolome provides a formidable analytical challenge. Here we describe a robust RPLC−MS method for identification and quantification of a diverse group of metabolites ranging from sugars, phosphosugars, and carboxylic acids to phosphocarboxylics acids, nucleotides, and coenzymes. This method is based on in vitro derivatization with a 13C-labeled tag that allows internal standard based quantification and enables separation of structural isomer pairs like glucose 6-phosphate and fructose 6-phosphate in a single chromatographic run. Calibration curves for individual metabolites showed linearity ranging over more than 2 orders of magnitude with correlation coefficients of R2 > 0.9975. The detection limits at a signal-to-noise ratio of 3 were below 1.0 μM (20 pmol) for most compounds. Thirty common metabolites involved in glycolysis, the pentose phosphate pathway, and tricarboxylic acid cycle were identified and quantified from yeast lysate with a relative standard deviation of less than 10%.

  详细分析细胞内代谢物是阐明细胞过程的关键组成部分。尽管反相液相色谱-质谱联用（RPLC-MS）的分辨率和灵活性使其成为代谢物分析中最强大的分析工具之一，但即使是简单的代谢组，其结构的多样性也带来了巨大的分析挑战。本文描述了一种稳健的RPLC-MS方法，用于鉴定和定量一系列广泛的代谢物，包括糖类、磷酸糖、羧酸、磷酸羧酸、核苷酸和辅酶。该方法基于使用13C标记标签的体外衍生化，允许基于内标的定量，并能在单次色谱运行中分离结构异构体对，如葡萄糖6-磷酸和果糖6-磷酸。单个代谢物的校准曲线显示线性范围超过两个数量级，相关系数R² > 0.9975。大多数化合物的信噪比为3的检测限低于1.0 μM（20 pmol）。从酵母裂解液中鉴定和定量了涉及糖酵解、戊糖磷酸途径和三羧酸循环的30种常见代谢物，相对标准偏差小于10%。
• The <i>Bacillus subtilis yqjI</i> Gene Encodes the NADP ⁺ -Dependent 6-P-Gluconate Dehydrogenase in the Pentose Phosphate Pathway
  作者：Nicola Zamboni、Eliane Fischer、Dietmar Laudert、Stéphane Aymerich、Hans-Peter Hohmann、Uwe Sauer

  DOI：10.1128/jb.186.14.4528-4534.2004

  日期：2004.7.15

  Despite the importance of the oxidative pentose phosphate (PP) pathway as a major source of reducing power and metabolic intermediates for biosynthetic processes, almost no direct genetic or biochemical evidence is available for Bacillus subtilis . Using a combination of knockout mutations in known and putative genes of the oxidative PP pathway and ¹³ C-labeling experiments, we demonstrated that yqjI encodes the NADP ⁺ -dependent 6-P-gluconate dehydrogenase, as was hypothesized previously from sequence similarities. Moreover, YqjI was the predominant isoenzyme during glucose and gluconate catabolism, and its role in the oxidative PP pathway could not be played by either of two homologues, GntZ and YqeC. This conclusion is in contrast to the generally held view that GntZ is the relevant isoform; hence, we propose a new designation for yqjI , gndA , the monocistronic gene encoding the principal 6-P-gluconate dehydrogenase. Although we demonstrated the NAD ⁺ -dependent 6-P-gluconate dehydrogenase activity of GntZ, gntZ mutants exhibited no detectable phenotype on glucose, and GntZ did not contribute to PP pathway fluxes during growth on glucose. Since gntZ mutants grew normally on gluconate, the functional role of GntZ remains obscure, as does the role of the third homologue, YqeC. Knockout of the glucose-6-P dehydrogenase-encoding zwf gene was primarily compensated for by increased glycolytic fluxes, but about 5% of the catabolic flux was rerouted through the gluconate bypass with glucose dehydrogenase as the key enzyme.

  摘要 尽管磷酸戊糖（PP）氧化途径是生物合成过程中还原力和代谢中间产物的主要来源，但几乎没有直接的遗传或生化证据表明 枯草芽孢杆菌 .通过对氧化磷酸戊糖（PP）途径的已知基因和推定基因进行基因敲除突变和 13 C 标记实验，我们证明了 yqjI 编码 NADP + -依赖的 6-P-葡萄糖酸脱氢酶。此外，YqjI 是葡萄糖和葡萄糖酸盐分解过程中最主要的同工酶，它在氧化 PP 途径中的作用无法由两个同源物 GntZ 和 YqeC 中的任何一个发挥。这一结论与人们普遍认为 GntZ 是相关同工酶的观点不同；因此，我们提出了一个新的名称，即 yqjI , gndA 即编码主要 6-P-葡萄糖酸脱氢酶的单核苷酸基因。尽管我们证明了 NAD + -依赖的 6-P-葡萄糖酸脱氢酶活性、 突变体 突变体在葡萄糖上没有表现出可检测到的表型，而且 GntZ 在葡萄糖上生长期间对 PP 通路通量没有贡献。由于 gntZ 突变体在葡萄糖酸盐上生长正常，因此 GntZ 的功能作用仍不明确，第三个同源物 YqeC 的作用也是如此。敲除编码葡萄糖-6-P脱氢酶的 zwf 基因的敲除主要通过糖酵解通量的增加来补偿，但约有 5%的分解代谢通量通过葡萄糖酸盐旁路转运，葡萄糖脱氢酶是其中的关键酶。
• Purification and properties of glucose-6-phosphate dehydrogenase (NADP+/NAD+) and 6-phosphogluconate dehydrogenase (NADP+/NAD+) from methanol-grown Pseudomonas C
  作者：Arie Ben-Bassat、Israel Goldberg

  DOI：10.1016/0005-2744(80)90036-4

  日期：1980.1

  Glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADPH+ 1-oxidoreductase, EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate:NADP+ 2-oxidoreductase, EC 1.1.1943) have been purified from methanol-grown Pseudomonas C. Glucose-6-phosphate dehydrogenase exhibits activity with either NADP+ or NAD+ as coenzymes, V NADP+ = 0.96 V NAD+.Km values of 22, 290, and 250 microns are

  6-磷酸葡萄糖脱氢酶（D-葡萄糖-6-磷酸：NADPH + 1-氧化还原酶，EC 1.1.1.49）和6-磷酸葡萄糖酸脱氢酶（6-磷酸-D-葡萄糖酸酯：NADP + 2-氧化还原酶，EC 1.1.1943）具有从甲醇生长的假单胞菌C中纯化得到.6-磷酸葡萄糖脱氢酶显示出以NADP +或NAD +作为辅酶的活性，V NADP + = 0.96 V NAD + .NADP +，NAD +和葡萄糖的Km值分别为22、290和250微米分别为6-磷酸酯（NADP +作为辅酶）。ATP以NAD +作为辅酶抑制Glc-6P脱氢酶的活性，而以DANP +抑制活性的程度较小。在存在MgCl 2的情况下，消除了Blc-6P脱氢geanase活性的ATP抑制作用。6-磷酸葡萄糖酸脱氢酶对NADP +或NAD +作为辅酶具有双重特异性，V NADP + = 1.66 V NAD + .Km值为20，对于NADP
• Crystal structure of Saccharomyces cerevisiae 6-phosphogluconate dehydrogenase Gnd1
  作者：Weiwei He、Yi Wang、Wei Liu、Cong-Zhao Zhou

  DOI：10.1186/1472-6807-7-38

  日期：2007.12

  As the third enzyme of the pentose phosphate pathway, 6-phosphogluconate dehydrogenase (6PGDH) is the main generator of cellular NADPH. Both thioredoxin reductase and glutathione reductase require NADPH as the electron donor to reduce oxidized thioredoxin or glutathione (GSSG). Since thioredoxin and GSH are important antioxidants, it is not surprising that 6PGDH plays a critical role in protecting cells from oxidative stress. Furthermore the activity of 6PGDH is associated with several human disorders including cancer and Alzheimer's disease. The 3D structural investigation would be very valuable in designing small molecules that target this enzyme for potential therapeutic applications.

  The crystal structure of 6-phosphogluconate dehydrogenase (6PGDH/Gnd1) from Saccharomyces cerevisiae has been determined at 2.37 Å resolution by molecular replacement. The overall structure of Gnd1 is a homodimer with three domains for each monomer, a Rossmann fold NADP⁺ binding domain, an all-α helical domain contributing the majority to hydrophobic interaction between the two subunits and a small C-terminal domain penetrating the other subunit. In addition, two citrate molecules occupied the 6PG binding pocket of each monomer. The intact Gnd1 had a Km of 50 ± 9 μM for 6-phosphogluconate and of 35 ± 6 μM for NADP⁺ at pH 7.5. But the truncated mutants without the C-terminal 35, 39 or 53 residues of Gnd1 completely lost their 6PGDH activity, despite remaining the homodimer in solution.

  The overall tertiary structure of Gnd1 is similar to those of 6PGDH from other species. The substrate and coenzyme binding sites are well conserved, either from the primary sequence alignment, or from the 3D structural superposition. Enzymatic activity assays suggest a sequential mechanism of catalysis, which is in agreement with previous studies. The C-terminal domain of Gnd1 functions as a hook to further tighten the dimer, but it is not necessary for the dimerization. This domain also works as a lid on the substrate binding pocket to control the binding of substrate and the release of product, so it is indispensable for the 6PGDH activity. Moreover, the co-crystallized citrate molecules, which mimic the binding mode of the substrate 6-phosphogluconate, provided us a novel strategy to design the 6PDGH inhibitors.

  摘要 背景：6-磷酸葡糖酸脱氢酶（6PGDH）是磷酸戊糖途径的第三个酶，是细胞NADPH的主要产生者。硫氧还蛋白还原酶和谷胱甘肽还原酶都需要NADPH作为电子供体来还原氧化的硫氧还蛋白或谷胱甘肽（GSSG）。由于硫氧还蛋白和GSH是重要的抗氧化剂，因此6PGDH在保护细胞免受氧化应激方面发挥着关键作用。此外，6PGDH的活性与几种人类疾病，包括癌症和阿尔茨海默病有关。三维结构研究将对设计针对该酶的小分子进行潜在治疗应用非常有价值。 结果：通过分子替代法，在2.37 Å的分辨率下确定了酵母菌（Saccharomyces cerevisiae）的6-磷酸葡糖酸脱氢酶（6PGDH/Gnd1）的晶体结构。Gnd1的整体结构是一个同源二聚体，每个单体有三个结构域，一个Rossmann折叠NADP+结合域，一个全部α螺旋结构域，为两个亚基之间的疏水相互作用做出了主要贡献，以及一个小的C末端结构域穿透另一个亚基。此外，两个柠檬酸分子占据了每个单体的6PG结合口袋。完整的Gnd1在pH 7.5下对6-磷酸葡糖酸和NADP+的Km分别为50±9μM和35±6μM。但是，缺少Gnd1的C末端35、39或53个残基的截短突变体完全失去了6PGDH活性，尽管在溶液中仍保持二聚体。 结论：Gnd1的整体三级结构类似于其他物种的6PGDH。底物和辅酶结合位点在主要序列比对或三维结构叠合中都很保守。酶活性测定表明，催化的顺序机制与以前的研究一致。Gnd1的C末端结构域起钩子作用，进一步紧密二聚体，但它对二聚体化并非必需。这个域还作为盖子控制底物结合口袋的盖子，以控制底物的结合和产物的释放，因此它对6PGDH活性是必不可少的。此外，共结晶的柠檬酸分子，模拟了底物6-磷酸葡糖酸的结合模式，为我们设计6PDGH抑制剂提供了一种新的策略。
• Conformational changes associated with cofactor/substrate binding of 6-phosphogluconate dehydrogenase from Escherichia coli and Klebsiella pneumoniae: Implications for enzyme mechanism
  作者：Ying-Yin Chen、Tzu-Ping Ko、Wei-Hung Chen、Li-Ping Lo、Chun-Hung Lin、Andrew H.-J. Wang

  DOI：10.1016/j.jsb.2009.08.006

  日期：2010.1

  6-Phosphogluconate dehydrogenase (6PGDH), the third enzyme of the pentose phosphate pathway, catalyzes the oxidative decarboxylation of 6-phosphogluconate, making ribulose 5-phosphate, along with the reduction of NADP(+) to NADPH and the release of CO(2). Here, we report the first apo-form crystal structure of the pathogenic Klebsiella pneumoniae 6PGDH (Kp6PGDH) and the structures of the highly homologous

  磷酸戊糖途径中的第三种酶6-磷酸葡萄糖酸脱氢酶（6PGDH）催化6-磷酸葡萄糖酸的氧化脱羧反应，生成核糖5-磷酸，同时将NADP（+）还原为NADPH并释放CO（2） ）。在这里，我们报告了致病性肺炎克雷伯菌6PGDH（Kp6PGDH）的第一个脱辅基晶体结构，以及与底物，底物/ NADPH和葡萄糖复合的高度同源的大肠杆菌K12 6PGDH（Ec6PGDH）的结构。NADPH与同型二聚体结构的一个亚基的结合触发了10度旋转，并导致辅酶结合域发生7A运动。因此，与相邻亚基的开放构象相反，辅酶被困在封闭的酶构象中。我们的Ec / Kp6PGDH结构与其他物种的结构的比较说明了辅酶结合后域构象如何受到影响，这反过来又引起了两个重要的与NADP（+）相互作用的氨基酸M14和N102的伴随运动。我们建议催化遵循有序的结合机制，在相应的亚基中交替构象变化，涉及几个相关的氨基酸残基。