Phosphohydroxypyruvate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Phosphohydroxypyruvate
• 英文别名: 2-oxo-3-phosphonatooxypropanoate
• 化学式: C3H2O7P-3
• 分子量: 181.02
• InChiKey: LFLUCDOSQPJJBE-UHFFFAOYSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  130
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Phosphohydroxypyruvate 、 水 生成 hydroxypyruvate 、 H3PO4
  参考文献：
  名称：

  Three serendipitous pathways in E. coli can bypass a block in pyridoxal‐5′‐phosphate synthesis

  摘要：

  Bacterial genomes encode hundreds to thousands of enzymes, most of which are specialized for particular functions. However, most enzymes have inefficient promiscuous activities, as well, that generally serve no purpose. Promiscuous reactions can be patched together to form multistep metabolic pathways. Mutations that increase expression or activity of enzymes in such serendipitous pathways can elevate flux through the pathway to a physiologically significant level. In this study, we describe the discovery of three serendipitous pathways that allow synthesis of pyridoxal‐5′‐phosphate (PLP) in a strain of E. coli that lacks 4‐phosphoerythronate (4PE) dehydrogenase (PdxB) when one of seven different genes is overexpressed. We have characterized one of these pathways in detail. This pathway diverts material from serine biosynthesis and generates an intermediate in the normal PLP synthesis pathway downstream of the block caused by lack of PdxB. Steps in the pathway are catalyzed by a protein of unknown function, a broad‐specificity enzyme whose physiological role is unknown, and a promiscuous activity of an enzyme that normally serves another function. One step in the pathway may be non‐enzymatic.

  DOI：

  10.1038/msb.2010.88
• 作为产物：
  描述：

  2-氧代-戊二酸离子(2-) 、 (2S)-2-amino-3-[hydroxy(oxido)phosphoryl]oxypropanoate 生成 Phosphohydroxypyruvate 、 2-氨基戊二酸酯
  参考文献：
  名称：

  4-磷酸-羟基-L-苏氨酸是大肠杆菌K-12中吡ido醛5'-磷酸辅酶生物合成的强制性中间体。

  摘要：

  我们显示，thrB编码的高丝氨酸激酶是在补充4-羟基-L-苏氨酸（同义词，3-羟基高丝氨酸）或D-羟乙醛的最小葡萄糖培养基上生长大肠杆菌K-12 pdxB突变体所必需的。该结果与其中吡咯醛5'-磷酸生物合成中的强制性中间体而不是4-羟基-L-苏氨酸的4-磷酸-羟基-L-苏氨酸（同义词，3-羟基高丝氨酸磷酸酯）的模型一致。作为第一个从头合成的B6-维生素，使用4-磷酸-羟基-L-苏氨酸作为底物的闭环会导致形成吡ido醇5'-磷酸而不是吡pyr醇。这些考虑表明，吡pyr醛5'-磷酸生物合成的主要从头途径不需要大肠杆菌吡ido醛/吡rid胺/吡rid醇激酶，

  DOI：

  10.1111/j.1574-6968.1996.tb08001.x

文献信息

• A novel alpha-ketoglutarate reductase activity of the serA-encoded 3-phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric aciduria
  作者：G Zhao、M E Winkler

  DOI：10.1128/jb.178.1.232-239.1996

  日期：1996.1

  alpha KG reductase was inhibited by Ser, D-HGA, 3PG, and glycine (Gly), whereas the D-HGA dehydrogenase was inhibited by Ser, alpha KG, 3-phosphohydroxypyruvate, and Gly. The implications of these findings for the regulation of Ser biosynthesis, the recycling of NADH, and the enzymology of 2-hydroxyacid dehydrogenases are discussed. Since the same pathway of Ser biosynthesis seems to be present in

  大肠杆菌serA编码的3-磷酸甘油酸（3PG）脱氢酶催化L-丝氨酸（Ser）生物合成的主要磷酸化途径的第一步。SerA酶在进化上与pdxB基因产物4-磷酸赤藓酸脱氢酶有关，该酶催化吡5醛5'-磷酸辅酶生物合成的一个分支中的第二步。Ser和吡ido醛5'-磷酸的生物合成途径在后续步骤中均使用serC（pdxF）编码的转氨酶。在对这些平行途径的分析中，我们尝试以反方向偶联转氨酶和脱氢酶反应。出乎意料的是，我们发现SerA酶催化了先前未发现的α-酮戊二酸（αKG）还原为2-羟基戊二酸（HGA）的还原反应。许多标准排除了这种SerA alpha KG还原酶活性是由底物或纯化的酶制剂中的污染引起的可能性。通过薄层色谱法和酶分析证实，HGA是SerAαKG还原酶反应的产物，显示HGA的D-异构体和L-异构体都是逆反应（脱氢酶）的底物。详细的稳态动力学分析表明，αKG的还原（表观Michaelis-Menten常数[Km（app）]
• 4-<i>O</i>-Phosphoryl-<scp>l</scp>-threonine, a substrate of the<i>pdx</i>C(<i>ser</i>C) gene product involved in vitamin B₆biosynthesis
  作者：Christel Drewke、Matthias Klein、Dorothee Clade、Ansgar Arenz、Rolf Müller、Eckhard Leistner

  DOI：10.1016/0014-5793(96)00652-7

  日期：1996.7.22

  Escherichia coli pdxC(serC) gene codes for a transaminase (EC 2.6.1.52). The gene is involved in both pyridoxine (vitamin B6) and serine biosynthesis and was over‐expressed as a MalE/PdxC(SerC) fusion protein. The fusion protein was purified by affinity chromatography on an amylose resin and hydrolyzed in the presence of protease factor Xa. Both the fusion protein and the PdxC(SerC) protein were characterized

  大肠杆菌 pdxC(serC) 基因编码转氨酶 (EC 2.6.1.52)。该基因参与吡哆醇（维生素 B6）和丝氨酸的生物合成，并作为 MalE/PdxC(SerC) 融合蛋白过表达。融合蛋白在直链淀粉树脂上通过亲和层析纯化，并在蛋白酶因子 Xa 存在下水解。融合蛋白和 PdxC(SerC) 蛋白都被表征（KM 值、周转数、最适 pH）。两种酶都使用 4-O-磷酰-l-苏氨酸而不是 4-羟基-l-苏氨酸作为底物，表明磷酸化而不是非磷酸化的氨基酸参与了吡哆醇的生物合成。磷酸吡哆醛被证明是这两种酶的辅助因子，因此似乎参与其自身的生物合成。
• Hirsch H.; Greenberg D.M., J Biol Chem, 1967, 0021-9258, 2283-7
  作者：Hirsch H.、Greenberg D.M.

  DOI：——

  日期：——
• PIZER L.I., J Biol Chem, 1963, 0021-9258, 3934-44
  作者：PIZER L.I.

  DOI：——

  日期：——
• Human Phosphoglycerate Dehydrogenase Produces the Oncometabolite <scp>d</scp>-2-Hydroxyglutarate
  作者：Jing Fan、Xin Teng、Ling Liu、Katherine R. Mattaini、Ryan E. Looper、Matthew G. Vander Heiden、Joshua D. Rabinowitz

  DOI：10.1021/cb500683c

  日期：2015.2.20

  Human d-3-phosphoglycerate dehydrogenase (PHGDH), the first enzyme in the serine biosynthetic pathway, is genomically amplified in tumors including breast cancer and melanoma. In PHGDH-amplified cancer cells, knockdown of PHGDH is not fully rescued by exogenous serine, suggesting possible additional growth-promoting roles for the enzyme. Here we show that, in addition to catalyzing oxidation of 3-phosphoglycerate, PHGDH catalyzes NADH-dependent reduction of α-ketoglutarate (AKG) to the oncometabolite d-2-hydroxyglutarate (d-2HG). Knockdown of PHGDH decreased cellular 2HG by approximately 50% in the PHGDH-amplified breast cancer cell lines MDA-MB-468 (normal concentration 93 μM) and BT-20 (normal concentration 35 μM) and overexpression of PHGDH increased cellular 2HG by over 2-fold in non-PHGDH-amplified MDA-MB-231 breast cancer cells, which normally display very low PHGDH expression. The reduced 2HG level in PHGDH knockdown cell lines can be rescued by PHGDH re-expression, but not by a catalytically inactive PHGDH mutant. The initial connection between cancer and d-2HG involved production of high levels of d-2HG by mutant isocitrate dehydrogenase. More recently, however, elevated d-2HG has been observed in breast cancer tumors without isocitrate dehydrogenase mutation. Our results suggest that PHGDH is one source of this d-2HG.