1-十七碳酰-甘油-3-磷酰胆碱 | 50930-23-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 中文名称: 1-十七碳酰-甘油-3-磷酰胆碱
• 英文名称: lysoPC(17:0)
• 英文别名: 17:0 lyso PC；1-Heptadecanoyl-sn-glycero-3-phosphocholine；[(2R)-3-heptadecanoyloxy-2-hydroxypropyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 50930-23-9
• 化学式: C₂₅H₅₂NO₇P
• 分子量: 509.664
• InChiKey: SRRQPVVYXBTRQK-XMMPIXPASA-N

物化性质

• 溶解度：
  乙醇：25mg/mL
• 物理描述：
  Solid
• 碰撞截面：
  237.7 Ų [M+HCOO]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  25
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• WGK Germany：
  3
• 海关编码：
  2923900090

反应信息

• 作为反应物：
  描述：

  1-十七碳酰-甘油-3-磷酰胆碱 在 Streptomyces chromofuscus phospholipase D 作用下， 生成 disodium 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate
  参考文献：
  名称：

  Evaluation of Inhibitory Actions of Flavonols and Related Substances on Lysophospholipase D Activity of Serum Autotaxin by a Convenient Assay Using a Chromogenic Substrate

  摘要：

  Overproduction of lysophosphatidic acid (LPA) by lysophospholipase D/autotaxin (lysoPLD/ATX) is postulated to be involved in the promotion of cancer and atherosclerosis. A lysoPLD inhibitor may be utilized to ameliorate the LPA-related pathological conditions. In this study, a new assay was devised to quantify p-nitrophenol from hydrolysis of chromogenic substrate by serum lysoPLD without tedious lipid extraction procedures. Flavonols, phenolic acids, free fatty acids, and N-acyltyrosines inhibited lysoPLD activity in a micromolar range. They were classified into competitive, noncompetitive, or mixed type inhibitors. The results show that the low hydrophobicity of an inhibitor is a critical factor in its preference for the binding to a noncatalytic binding site over a catalytic binding site. Considering its reported bioavailability and the low dependency of its inhibitory activity on serum dilution, flavonol is likely to be a more effective lysoPLD inhibitor in human blood circulation in vivo than the other inhibitors including LPA.

  DOI：

  10.1021/jf904155a
• 作为产物：
  描述：

  1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine 、 水 生成 Arachidonate 、 1-十七碳酰-甘油-3-磷酰胆碱 、 氢(+1)阳离子
  参考文献：
  名称：

  Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay

  摘要：

  ABHD16A 是催化磷脂酰丝氨酸（PS）产生溶菌-PS 的主要酶。一种新的 ABHD16A 抑制剂和基因敲除小鼠表明，在炎症期间，ABHD16A 和与疾病相关的 ABHD12（一种降解溶血磷脂的酶）之间会发生动态的相互作用。ABHD16A 被确定为催化磷脂酰丝氨酸（PS）产生溶菌-PS 的主要酶。一种新的 ABHD16A 抑制剂和基因敲除小鼠显示，在炎症期间，ABHD16A 和与疾病相关的 ABHD12（一种降解溶菌磷-PS 的酶）之间会发生动态的相互作用。 溶血磷脂酰丝氨酸（溶血磷脂酰丝氨酸）是一类调节免疫和神经过程的信号脂质。人们对溶血磷脂酰丝氨酸的体内代谢仍然知之甚少。最近，我们确定 ABHD12 是一种主要的脑溶菌-多糖脂酶，这表明溶菌-多糖与多发性神经病、听力损失、共济失调、色素性视网膜炎和白内障（PHARC）等神经系统疾病有关。在这里，我们将基于活性的分析与药理学和遗传学方法相结合，将特征不清的 ABHD16A 酶注释为一种磷脂酰丝氨酸（PS）脂肪酶，它能在哺乳动物系统中生成溶血磷脂。我们描述了一种 ABHD16A 的小分子抑制剂，它能从细胞（包括从 PHARC 患者身上提取的淋巴母细胞）中消耗溶血磷脂。在小鼠巨噬细胞中，破坏 ABHD12 和 ABHD16A 会分别增加和减少溶菌-多糖和脂多糖诱导的细胞因子的产生。最后，Abhd16aâ/â小鼠脑溶菌-PS减少，这与Abhd12â/â小鼠溶菌-PS的增加相反。我们的发现揭示了 ABHD16A-ABHD12 轴动态调节体内溶菌-多糖代谢的过程，并将这些酶指定为治疗神经免疫疾病的潜在靶点。

  DOI：

  10.1038/nchembio.1721

文献信息

• Evaluation of Inhibitory Actions of Flavonols and Related Substances on Lysophospholipase D Activity of Serum Autotaxin by a Convenient Assay Using a Chromogenic Substrate
  作者：Kaori Ueda、Masanori Yoshihara、Michiyasu Nakao、Tamotsu Tanaka、Shigeki Sano、Kenji Fukuzawa、Akira Tokumura

  DOI：10.1021/jf904155a

  日期：2010.5.26

  Overproduction of lysophosphatidic acid (LPA) by lysophospholipase D/autotaxin (lysoPLD/ATX) is postulated to be involved in the promotion of cancer and atherosclerosis. A lysoPLD inhibitor may be utilized to ameliorate the LPA-related pathological conditions. In this study, a new assay was devised to quantify p-nitrophenol from hydrolysis of chromogenic substrate by serum lysoPLD without tedious lipid extraction procedures. Flavonols, phenolic acids, free fatty acids, and N-acyltyrosines inhibited lysoPLD activity in a micromolar range. They were classified into competitive, noncompetitive, or mixed type inhibitors. The results show that the low hydrophobicity of an inhibitor is a critical factor in its preference for the binding to a noncatalytic binding site over a catalytic binding site. Considering its reported bioavailability and the low dependency of its inhibitory activity on serum dilution, flavonol is likely to be a more effective lysoPLD inhibitor in human blood circulation in vivo than the other inhibitors including LPA.
• Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay
  作者：Siddhesh S Kamat、Kaddy Camara、William H Parsons、Dong-Hui Chen、Melissa M Dix、Thomas D Bird、Amy R Howell、Benjamin F Cravatt

  DOI：10.1038/nchembio.1721

  日期：2015.2

  ABHD16A is identified as a major enzyme catalyzing production of lyso-PS from phosphatidylserine (PS). A new ABHD16A inhibitor and knockout mice show a dynamic interplay occurring during inflammation between ABHD16A and disease-linked ABHD12, an enzyme that degrades lyso-PS. ABHD16A is identified as a major enzyme catalyzing production of lyso-PS from phosphatidylserine (PS). A new ABHD16A inhibitor and knockout mice show a dynamic interplay occurring during inflammation between ABHD16A and disease-linked ABHD12, an enzyme that degrades lyso-PS. Lysophosphatidylserines (lyso-PSs) are a class of signaling lipids that regulate immunological and neurological processes. The metabolism of lyso-PSs remains poorly understood in vivo. Recently, we determined that ABHD12 is a major brain lyso-PS lipase, implicating lyso-PSs in the neurological disease polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC), which is caused by null mutations in the ABHD12 gene. Here, we couple activity-based profiling with pharmacological and genetic methods to annotate the poorly characterized enzyme ABHD16A as a phosphatidylserine (PS) lipase that generates lyso-PS in mammalian systems. We describe a small-molecule inhibitor of ABHD16A that depletes lyso-PSs from cells, including lymphoblasts derived from subjects with PHARC. In mouse macrophages, disruption of ABHD12 and ABHD16A respectively increases and decreases both lyso-PSs and lipopolysaccharide-induced cytokine production. Finally, Abhd16a−/− mice have decreased brain lyso-PSs, which runs counter to the elevation in lyso-PS in Abhd12−/− mice. Our findings illuminate an ABHD16A-ABHD12 axis that dynamically regulates lyso-PS metabolism in vivo, designating these enzymes as potential targets for treating neuroimmunological disorders.

  ABHD16A 是催化磷脂酰丝氨酸（PS）产生溶菌-PS 的主要酶。一种新的 ABHD16A 抑制剂和基因敲除小鼠表明，在炎症期间，ABHD16A 和与疾病相关的 ABHD12（一种降解溶血磷脂的酶）之间会发生动态的相互作用。ABHD16A 被确定为催化磷脂酰丝氨酸（PS）产生溶菌-PS 的主要酶。一种新的 ABHD16A 抑制剂和基因敲除小鼠显示，在炎症期间，ABHD16A 和与疾病相关的 ABHD12（一种降解溶菌磷-PS 的酶）之间会发生动态的相互作用。 溶血磷脂酰丝氨酸（溶血磷脂酰丝氨酸）是一类调节免疫和神经过程的信号脂质。人们对溶血磷脂酰丝氨酸的体内代谢仍然知之甚少。最近，我们确定 ABHD12 是一种主要的脑溶菌-多糖脂酶，这表明溶菌-多糖与多发性神经病、听力损失、共济失调、色素性视网膜炎和白内障（PHARC）等神经系统疾病有关。在这里，我们将基于活性的分析与药理学和遗传学方法相结合，将特征不清的 ABHD16A 酶注释为一种磷脂酰丝氨酸（PS）脂肪酶，它能在哺乳动物系统中生成溶血磷脂。我们描述了一种 ABHD16A 的小分子抑制剂，它能从细胞（包括从 PHARC 患者身上提取的淋巴母细胞）中消耗溶血磷脂。在小鼠巨噬细胞中，破坏 ABHD12 和 ABHD16A 会分别增加和减少溶菌-多糖和脂多糖诱导的细胞因子的产生。最后，Abhd16aâ/â小鼠脑溶菌-PS减少，这与Abhd12â/â小鼠溶菌-PS的增加相反。我们的发现揭示了 ABHD16A-ABHD12 轴动态调节体内溶菌-多糖代谢的过程，并将这些酶指定为治疗神经免疫疾病的潜在靶点。