1-Arachidonoyl-sn-glycero-3-phosphocholine | 60701-99-7

• 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: 1-Arachidonoyl-sn-glycero-3-phosphocholine
• 英文别名: [(2R)-2-hydroxy-3-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 60701-99-7
• 化学式: C28H50NO7P
• 分子量: 543.7
• InChiKey: LAXQYRRMGGEGOH-JXRLJXCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  24
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-Arachidonoyl-sn-glycero-3-phosphocholine 、 水 生成 Arachidonate 、 氢(+1)阳离子 、 甘磷酸胆碱
  参考文献：
  名称：

  The Highly Selective Production of 2-Arachidonoyl Lysophosphatidylcholine Catalyzed by Purified Calcium-independent Phospholipase A2γ

  摘要：

  Herein, we report the heterologous expression of the human peroxisomal 63-kDa calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) isoform in Sf9 cells, purification of the N-terminal His-tagged enzyme by affinity chromatography, and the identification of its remarkable substrate selectivity that results in the highly selective generation of 2-arachidonoyl lysophosphatidylcholine. Mass spectrometric analyses demonstrated that purified iPLA(2)gamma hydrolyzed saturated or monounsaturated aliphatic groups readily from either the sn-1 or sn-2 positions of phospholipids. In addition, purified iPLA(2)gamma effectively liberated arachidonic acid from the sn-2 position of plasmenylcholine substrates. In contrast, incubation of iPLA(2)gamma with 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine resulted in the rapid release of palmitic acid and the selective accumulation of 2-arachidonoyl lysophosphatidylcholine (LPC), which was not metabolized further by iPLA(2)gamma. The putative regiospecificity of the 2-arachidonoyl LPC product was authenticated by its diagnostic fragmentation pattern during tandem mass spectrometric analysis. To identify the physiological relevance of iPLA(2)gamma-mediated 2-arachidonoyl LPC production utilizing naturally occurring membranes, we incubated purified rat hepatic peroxisomes with iPLA(2)gamma and similarly identified the selective accumulation of 2-arachidonoyl LPC. Furthermore, tandem mass spectrometric analysis demonstrated that 2-arachidonoyl LPC is a natural product in human myocardium, a tissue in which iPLA(2)gamma expression is robust. Because 2-arachidonoyl LPC represents a key branch point intermediate that can potentially lead to a variety of bioactive molecules in eicosanoid signaling (e.g. arachidonic acid, 2-arachidonoylglycerol), these results have uncovered a novel eicosanoid selective pathway through iPLA(2)gamma-mediated 2-arachidonoyl LPC production to amplify and diversify the repertoire of biologic lipid second messengers in response to cellular stimulation.

  DOI：

  10.1074/jbc.m502358200
• 作为产物：
  描述：

  PC(20:4(5Z,8Z,11Z,14Z)/16:0) 、 水 生成 1-Arachidonoyl-sn-glycero-3-phosphocholine 、 氢(+1)阳离子 、 十六烷酸酯
  参考文献：
  名称：

  人胞质85 kDa磷脂酶A2的多种酶活性：水解反应和酰基转移至甘油。

  摘要：

  当在甘油存在下进行测定时，重组人85 kDa胞质磷脂酶A2（cPLA2）除了水解这些底物外，还催化了放射性标记的磷脂酰胆碱和脂肪酸的对位取代苯基酯的酰基链向甘油的转移。转酰化反应的产物是单酰基甘油（MAG），且酰基链主要被酯化（>或= 95％）为甘油的伯羟基（sn-1 / 3）；立体化学未知。通过为酶-底物复合物形成产物提供额外的机械途径，以及通过增加酶的固有水解和转酰化活性，甘油的浓度都加速了酶的转化。测定了sn-1 / 3-花生四烯酸单酰基甘油的明显酶水解，而sn-1 /3-α-亚麻酸-和sn-2-花生四烯酸单酰基甘油未检测到水解。1,3-丙二醇也可作为酶的酰基受体。cPLA2水解缺少sn-2羟基的溶血磷脂酰胆碱的类似物。该酶将水解rac-1-（花生四烯基，α-亚麻酸，棕榈酰）-2-O-十六烷基-甘油-3-磷酸胆碱脂质的sn-1-酰基链，并将该酰基链转移至甘油。因此，cPLA2具有磷脂

  DOI：

  10.1021/bi00024a004

文献信息

• Biochemical and Molecular Characterization of a Novel Choline-specific Glycerophosphodiester Phosphodiesterase Belonging to the Nucleotide Pyrophosphatase/Phosphodiesterase Family
  作者：Hideki Sakagami、Junken Aoki、Yumiko Natori、Kiyotaka Nishikawa、Yoshiyuki Kakehi、Yasuhiro Natori、Hiroyuki Arai

  DOI：10.1074/jbc.m413438200

  日期：2005.6

  Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that release nucleoside 5'-monophosphate from a variety of nucleotides and nucleotide derivatives. The mammalian NPP family comprises seven members, but only three of these (NPP1-3) have been studied in some detail. Previously we showed that lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid, is identical to NPP2. More recently an uncharacterized novel NPP member (NPP7) was shown to have alkaline sphingomyelinase activity. These findings raised the possibility that other members of the NPP family act on phospholipids. Here we show that the sixth member of the NPP family, NPP6, is a choline-specific glycerophosphodiester phosphodiesterase. The sequence of NPP6 encodes a transmembrane protein containing an NPP domain with significant homology to NPP4, NPP5, and NPP7/alkaline sphingomyelinase. When expressed in HeLa cells, NPP6 was detected in both the cells and the cell culture medium as judged by Western blotting and by enzymatic activity. Recombinant NPP6 efficiently hydrolyzed the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine, but not the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'-monophosphate. In addition, NPP6 hydrolyzed LPC to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. NPP6 showed a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. It also hydrolyzed glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. In mice, NPP6 mRNA was predominantly detected in kidney with a lesser expression in brain and heart, and in human it was detected in kidney and brain. The present results suggest that NPP6 has a specific role through the hydrolysis of polyunsaturated LPC, glycerophosphorylcholine, or sphingosylphosphorylcholine in these organs.
• Identification of Human Plasma Lysophospholipase D, a Lysophosphatidic Acid-producing Enzyme, as Autotaxin, a Multifunctional Phosphodiesterase
  作者：Akira Tokumura、Eiji Majima、Yuko Kariya、Kyoko Tominaga、Kentaro Kogure、Katsuhiko Yasuda、Kenji Fukuzawa

  DOI：10.1074/jbc.m205623200

  日期：2002.10

  We purified human plasma lysophospholipase D that produces physiologically active lysophosphatidic acid and showed that it is a soluble form of autotaxin, an ecto-nucleotide pyrophosphatase/phosphodiesterase, originally found as a tumor cell motility-stimulating factor. Its lower K-m value for a lysophosphatidylcholine than that for a synthetic substrate of nucleotide suggests that lysophosphatidylcholine is a more likely physiological substrate for autotaxin and that its predicted physiological and pathophysiological functions could be mediated by its activity to produce lysophosphate acid, an intercellular mediator. Recombinant autotaxin was found to have lysophospholipase D activity; its substrate specificity and metal ion requirement were the same as those of the purified plasma enzyme. The activity of lysophospholipase, D for exogenous lysophosphatidylcholine in human serum was found to increase in normal pregnant women at the third trimester of pregnancy and to a higher extent in patients in threatened preterm delivery, suggesting its roles in induction of parturition.
• The Highly Selective Production of 2-Arachidonoyl Lysophosphatidylcholine Catalyzed by Purified Calcium-independent Phospholipase A2γ
  作者：Wei Yan、Christopher M. Jenkins、Xianlin Han、David J. Mancuso、Harold F. Sims、Kui Yang、Richard W. Gross

  DOI：10.1074/jbc.m502358200

  日期：2005.7

  Herein, we report the heterologous expression of the human peroxisomal 63-kDa calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) isoform in Sf9 cells, purification of the N-terminal His-tagged enzyme by affinity chromatography, and the identification of its remarkable substrate selectivity that results in the highly selective generation of 2-arachidonoyl lysophosphatidylcholine. Mass spectrometric analyses demonstrated that purified iPLA(2)gamma hydrolyzed saturated or monounsaturated aliphatic groups readily from either the sn-1 or sn-2 positions of phospholipids. In addition, purified iPLA(2)gamma effectively liberated arachidonic acid from the sn-2 position of plasmenylcholine substrates. In contrast, incubation of iPLA(2)gamma with 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine resulted in the rapid release of palmitic acid and the selective accumulation of 2-arachidonoyl lysophosphatidylcholine (LPC), which was not metabolized further by iPLA(2)gamma. The putative regiospecificity of the 2-arachidonoyl LPC product was authenticated by its diagnostic fragmentation pattern during tandem mass spectrometric analysis. To identify the physiological relevance of iPLA(2)gamma-mediated 2-arachidonoyl LPC production utilizing naturally occurring membranes, we incubated purified rat hepatic peroxisomes with iPLA(2)gamma and similarly identified the selective accumulation of 2-arachidonoyl LPC. Furthermore, tandem mass spectrometric analysis demonstrated that 2-arachidonoyl LPC is a natural product in human myocardium, a tissue in which iPLA(2)gamma expression is robust. Because 2-arachidonoyl LPC represents a key branch point intermediate that can potentially lead to a variety of bioactive molecules in eicosanoid signaling (e.g. arachidonic acid, 2-arachidonoylglycerol), these results have uncovered a novel eicosanoid selective pathway through iPLA(2)gamma-mediated 2-arachidonoyl LPC production to amplify and diversify the repertoire of biologic lipid second messengers in response to cellular stimulation.
• Multiple Enzymic Activities of the Human Cytosolic 85-kDa Phospholipase A2: Hydrolytic Reactions and Acyl Transfer to Glycerol
  作者：Arthur M. Hanel、Michael H. Gelb

  DOI：10.1021/bi00024a004

  日期：1995.6.20

  incorporated into 1,2-ditetradecyl-sn-glycero-3-phosphomethanol/Triton X-100 mixed micelles as substrates for the transacylation/hydrolysis reactions of the enzyme. Average product ratios, which are defined as the amount of monoacylglycerol formed to phenyl ester hydrolyzed, were 2.1 +/- 0.1 (n = 5) for the para-substituted phenyl esters and 2.0 +/- 0.3 (n = 7) for phenyl alpha-linolenate. The similarity of

  当在甘油存在下进行测定时，重组人85 kDa胞质磷脂酶A2（cPLA2）除了水解这些底物外，还催化了放射性标记的磷脂酰胆碱和脂肪酸的对位取代苯基酯的酰基链向甘油的转移。转酰化反应的产物是单酰基甘油（MAG），且酰基链主要被酯化（>或= 95％）为甘油的伯羟基（sn-1 / 3）；立体化学未知。通过为酶-底物复合物形成产物提供额外的机械途径，以及通过增加酶的固有水解和转酰化活性，甘油的浓度都加速了酶的转化。测定了sn-1 / 3-花生四烯酸单酰基甘油的明显酶水解，而sn-1 /3-α-亚麻酸-和sn-2-花生四烯酸单酰基甘油未检测到水解。1,3-丙二醇也可作为酶的酰基受体。cPLA2水解缺少sn-2羟基的溶血磷脂酰胆碱的类似物。该酶将水解rac-1-（花生四烯基，α-亚麻酸，棕榈酰）-2-O-十六烷基-甘油-3-磷酸胆碱脂质的sn-1-酰基链，并将该酰基链转移至甘油。因此，cPLA2具有磷脂