L-Glycerin-3-phosphat

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 英文名称: L-Glycerin-3-phosphat
• 英文别名: glycerol 3-phosphate；Sn-glycerol 3-phosphate(2-)；[(2R)-2,3-dihydroxypropyl] phosphate
• 化学式: C₃H₇O₆P
• 分子量: 170.059
• InChiKey: AWUCVROLDVIAJX-GSVOUGTGSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-Glycerin-3-phosphat 在 氧气 作用下， 以 水 为溶剂， 生成 1,3-dihydroxyacetone phosphate
  参考文献：
  名称：

  Fessner, Wolf-Dieter; Sinerius, Gudrun, Angewandte Chemie, 1994, vol. 106, # 2, p. 217 - 220

  摘要：

  DOI：
• 作为产物：
  描述：

  水 、 甘磷酸胆碱 生成 胆碱 、 氢(+1)阳离子 、 L-Glycerin-3-phosphat
  参考文献：
  名称：

  GDPD5 is a glycerophosphocholine phosphodiesterase that osmotically regulates the osmoprotective organic osmolyte GPC

  摘要：

  甘油磷酸胆碱（GPC）是一种丰富的渗透保护肾髓质有机渗透物。我们之前发现，它从磷脂酰胆碱合成，由神经病变靶标酯酶的渗透调节活性催化。我们还发现，它的降解由甘油磷酸胆碱磷二酸二酯酶（GPC-PDE）活性催化，而将渗透压从300升高到500摩尔/千克，通过添加NaCl或尿素，抑制GPC-PDE活性，从而导致GPC的增加。在本研究中，我们确定了GDPD5（含有甘油磷酸二酯酶结构域的磷酸二酯酶）作为GPC-PDE，它被高NaCl或尿素迅速抑制。重组GDPD5与神经病变靶标酯酶共定位于HEK293细胞的周核区域，并且免疫沉淀的重组GDPD5在体外降解GPC。当从GDPD5免疫沉淀的细胞暴露于高NaCl或尿素时，体外活性降低。此外，高NaCl通过增加降解速率降低了GDPD5的mRNA丰度，而高尿素则没有。在300摩尔/千克的情况下，GDPD5的siRNA敲低增加了小鼠内侧髓质集合管3细胞中的GPC，而重组GDPD5的过表达增加了细胞GPC-PDE活性，伴随着GPC的降低。我们得出结论，GDPD5是一种GPC-PDE，有助于细胞GPC的渗透调节。

  DOI：

  10.1073/pnas.0805496105

文献信息

• Steady-State Kinetics of Reduction of Coenzyme Q Analogs by Glycerol-3-phosphate Dehydrogenase in Brown Adipose Tissue Mitochondria
  作者：Hana Rauchová、Romana Fato、Zdenek Drahota、Giorgio Lenaz

  DOI：10.1006/abbi.1997.0150

  日期：1997.8

  We have undertaken a study of the role of coenzyme Q (CoQ) in glycerol-3-phosphate oxidation in mitochondrial membranes from hamster brown adipose tissue, using either quinone homologs, as CoQ1 and CoQ2, or the analogs duroquinone and decylubiquinone as artificial electron acceptors. We have found that the most suitable electron acceptor for glycerol-3-phosphate:CoQ reductase activity in situ in the

  我们已经研究了辅酶Q（CoQ）在仓鼠棕色脂肪组织线粒体膜中甘油3-磷酸甘油氧化中的作用，使用醌同系物作为CoQ1和CoQ2，或类似物duroquinone和decylubiquinone作为人工电子受体。我们已经发现，最适合线粒体膜中3-磷酸甘油：CoQ还原酶活性的电子受体是同源CoQ1，它产生最高的酶活性速率（225 +/- 41 nmol x min（-1）x mg（-1）蛋白）。在测试了所有受体后，醌还原速率对Complex III抑制剂完全不敏感，这表明相对于内源CoQ库，所有受体都易于进入脱氢酶的醌结合位点，以使络合物III保持在氧化状态的方式。我们还通过逐步戊烷萃取棕色脂肪组织线粒体的实验研究了内源CoQ（70％CoQ9和30％CoQ10的混合物的1.35 nmol / mg蛋白）的饱和动力学，发现了K（m）的积分活性内源性辅酶Q0.2的3-磷酸甘油细胞色素C还原酶，表明3-磷
• Aerobic sn-glycerol-3-phosphate dehydrogenase from Escherichia coli binds to the cytoplasmic membrane through an amphipathic α-helix
  作者：Antje-Christine WALZ、Rudy A. DEMEL、Ben de KRUIJFF、Rupert MUTZEL

  DOI：10.1042/bj20011853

  日期：2002.7.15

  sn-Glycerol-3-phosphate dehydrogenase (GlpD) from Escherichia coli is a peripheral membrane enzyme involved in respiratory electron transfer. For it to display its enzymic activity, binding to the inner membrane is required. The way the enzyme interacts with the membrane and how this controls activity has not been elucidated. In the present study we provide evidence for direct protein—lipid interaction. Using the monolayer technique, we observed insertion of GlpD into lipid monolayers with a clear preference for anionic phospholipids. GlpD variants with point mutations in their predicted amphipathic helices showed a decreased ability to penetrate anionic phospholipid monolayers. From these data we propose that membrane binding of GlpD occurs by insertion of an amphipathic helix into the acyl-chain region of lipids mediated by negatively charged phospholipids.

  大肠杆菌的甘油-3-磷酸脱氢酶（GlpD）是一种外周膜酶，参与呼吸电子传递。它需要与内膜结合才能显示其酶活性。该酶与膜相互作用的方式以及如何控制其活性尚未阐明。在本研究中，我们提供了蛋白质与脂质直接相互作用的证据。利用单层技术，我们观察到 GlpD 插入脂质单层，并明显偏好阴离子磷脂。GlpD变体的预测两性螺旋发生点突变后，其穿透阴离子磷脂单层的能力下降。根据这些数据，我们认为 GlpD 的膜结合是由带负电荷的磷脂介导的两性螺旋插入脂质的酰基链区域而发生的。
• GDPD5 is a glycerophosphocholine phosphodiesterase that osmotically regulates the osmoprotective organic osmolyte GPC
  作者：Morgan Gallazzini、Joan D. Ferraris、Maurice B. Burg

  DOI：10.1073/pnas.0805496105

  日期：2008.8.5

  Glycerophosphocholine (GPC) is an abundant osmoprotective renal medullary organic osmolyte. We previously found that its synthesis from phosphatidylcholine is catalyzed by tonicity-regulated activity of the phospholipase B, neuropathy target esterase. We also found that its degradation is catalyzed by glycerophosphocholine phosphodiesterase (GPC-PDE) activity and that elevating osmolality from 300 to 500 mosmol/kg by adding NaCl or urea, inhibits GPC-PDE activity, which contributes to the resultant increase of GPC. In the present studies we identify GDPD5 (glycerophosphodiester phosphodiesterase domain containing 5) as a GPC-PDE that is rapidly inhibited by high NaCl or urea. Recombinant GDPD5 colocalizes with neuropathy target esterase in the perinuclear region of HEK293 cells, and immuno-precipitated recombinant GDPD5 degrades GPC in vitro . The in vitro activity is reduced when the cells from which the GDPD5 is immuno-precipitated have been exposed to high NaCl or urea. In addition, high NaCl decreases mRNA abundance of GDPD5 via an increase of its degradation rate, although high urea does not. At 300 mosmol/kg siRNA knockdown of GDPD5 increases GPC in mouse inner medullary collecting duct-3 cells, and over expression of recombinant GDPD5 increases cellular GPC-PDE activity, accompanied by decreased GPC. We conclude that GDPD5 is a GPC-PDE that contributes to osmotic regulation of cellular GPC.

  甘油磷酸胆碱（GPC）是一种丰富的渗透保护肾髓质有机渗透物。我们之前发现，它从磷脂酰胆碱合成，由神经病变靶标酯酶的渗透调节活性催化。我们还发现，它的降解由甘油磷酸胆碱磷二酸二酯酶（GPC-PDE）活性催化，而将渗透压从300升高到500摩尔/千克，通过添加NaCl或尿素，抑制GPC-PDE活性，从而导致GPC的增加。在本研究中，我们确定了GDPD5（含有甘油磷酸二酯酶结构域的磷酸二酯酶）作为GPC-PDE，它被高NaCl或尿素迅速抑制。重组GDPD5与神经病变靶标酯酶共定位于HEK293细胞的周核区域，并且免疫沉淀的重组GDPD5在体外降解GPC。当从GDPD5免疫沉淀的细胞暴露于高NaCl或尿素时，体外活性降低。此外，高NaCl通过增加降解速率降低了GDPD5的mRNA丰度，而高尿素则没有。在300摩尔/千克的情况下，GDPD5的siRNA敲低增加了小鼠内侧髓质集合管3细胞中的GPC，而重组GDPD5的过表达增加了细胞GPC-PDE活性，伴随着GPC的降低。我们得出结论，GDPD5是一种GPC-PDE，有助于细胞GPC的渗透调节。
• 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。
• GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors
  作者：Bin Zheng、Christopher P. Berrie、Daniela Corda、Marilyn G. Farquhar

  DOI：10.1073/pnas.0337605100

  日期：2003.2.18

  Previously we identified MIR16 (membrane interacting protein of RGS16) as an integral membrane glycoprotein that interacts with regulator of G protein signaling proteins and shares significant sequence homology with bacterial glycerophosphodiester phosphodiesterases (GDEs), suggesting that it is a putative mammalian GDE. Here we show that MIR16 belongs to a large, evolutionarily conserved family of GDEs with a characteristic putative catalytic domain that shares a common motif (amino acids 92–116) with the catalytic domains of mammalian phosphoinositide phospholipases C. Expression of wild-type MIR16 (renamed GDE1), but not two catalytic domain mutants (E97A/D99A and H112A), leads to a dramatic increase in glycerophosphoinositol phosphodiesterase (GPI-PDE) activity in HEK 293T cells. Analysis of substrate specificity shows that GDE1/MIR16 selectively hydrolyzes GPI over glycerophosphocholine. The GPI-PDE activity of GDE1/MIR16 expressed in HEK 293T cells can be regulated by stimulation of G protein-coupled, α/β-adrenergic, and lysophospholipid receptors. Membrane topology studies suggest a model in which the catalytic GDE domain faces the lumen/extracellular space and the C terminus faces the cytoplasm. Our results suggest that by serving as a PDE for GPI with its activity regulated by G protein signaling, GDE1/MIR16 provides a link between phosphoinositide metabolism and G protein signal transduction.

  我们之前已经确认MIR16（RGS16膜相互作用蛋白）是一种与G蛋白信号调节蛋白相互作用的整合膜糖蛋白，与细菌甘油磷酸二酯磷酸二酯酶（GDEs）具有显著的序列同源性，暗示它是一种可能的哺乳动物GDE。在这里，我们展示MIR16属于一个大的、进化上保守的GDE家族，具有一个特征性的潜在催化域，该域与哺乳动物磷脂酰肌醇磷脂酶C的催化域共享一个常见的基序（氨基酸92-116）。表达野生型MIR16（改名为GDE1），但不是两个催化域突变体（E97A/D99A和H112A），会导致HEK 293T细胞中甘油磷肌醇磷酸二酯酶（GPI-PDE）活性的显著增加。底物特异性分析表明，GDE1/MIR16选择性水解GPI而不是甘油磷胆碱。在HEK 293T细胞中表达的GDE1/MIR16的GPI-PDE活性可以通过激活G蛋白偶联的α/β肾上腺素能和溶血磷脂受体来调节。膜拓扑研究表明，催化GDE域面向腔室/细胞外空间，C端面向细胞质。我们的结果表明，通过作为G蛋白信号调节的PDE，针对GPI的GDE1/MIR16提供了磷脂酰肌醇代谢和G蛋白信号转导之间的联系。