N,1,2-trioleoyl-sn-glycero-3-phosphoethanolamine(1-)

• 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: N,1,2-trioleoyl-sn-glycero-3-phosphoethanolamine(1-)
• 英文别名: [(2R)-2,3-bis[[(Z)-octadec-9-enoyl]oxy]propyl] 2-[[(Z)-octadec-9-enoyl]amino]ethyl phosphate
• 化学式: C59H109NO9P-
• 分子量: 1007.5
• InChiKey: FKSBBLIERCUNPB-WTZXFCJFSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  20.5
• 重原子数：
  70
• 可旋转键数：
  57
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  水 、 N,1,2-trioleoyl-sn-glycero-3-phosphoethanolamine(1-) 生成 Dioleoyl phosphatidate 、 氢(+1)阳离子 、 油酰乙醇胺
  参考文献：
  名称：

  作为金属β-内酰胺酶家族成员的纯化生成anandamide的磷脂酶D的功能分析。

  摘要：

  在动物组织中，通过催化属于金属β-内酰胺酶家族的特定磷脂酶D（NAPE-PLD），由其相应的N-酰基磷脂酰乙醇胺（NAPE）形成了包括内源性大麻素anandamide在内的生物活性N-酰基乙醇胺。尽管其潜在的生理重要性，但NAPE-PLD尚未通过纯化的酶制剂进行表征。在本研究中，我们在大肠杆菌中表达了重组NAPE-PLD，并对其进行了高度纯化。纯化的酶被毫摩尔浓度的Mg2 +以及Ca2 +以剂量依赖性方式显着激活，因此似乎具有组成性活性。该酶对各种甘油磷脂之间的NAPEs表现出极高的特异性，但对不同的NAPEs长链或中链N-酰基物种没有明显的选择性。这些结果表明NAPE-PLD降解不同NAPE的能力而不会损害其他膜磷脂。金属分析表明，NAPE-PLD中存在催化重要的锌。此外，定点诱变研究针对NAPE-PLD的几个组氨酸和天冬氨酸残基，这些残基在金属β-内酰胺酶家族中高度保守。Asp-147

  DOI：

  10.1074/jbc.m512359200
• 作为产物：
  描述：

  二油酰基 L-α-磷脂酰乙醇胺 生成 2-azaniumylethyl (2R)-3-hydroxy-2-[(9Z)-octadec-9-enoyloxy]propyl phosphate 、 氢(+1)阳离子 、 N,1,2-trioleoyl-sn-glycero-3-phosphoethanolamine(1-)
  参考文献：
  名称：

  钙依赖性酰基转移酶，可产生N-酰基磷脂酰乙醇胺

  摘要：

  30年前，人们描述了一种钙依赖性酶活性，可产生N-酰基磷脂酰乙醇胺（NAPE），N-酰基磷脂酰乙醇胺是N-酰基乙醇胺（NAE）脂质递质的前体，包括内源性大麻素anandamide。这种依赖钙的N-酰基转移酶（Ca-NAT）的身份一直很神秘。在这里，我们使用基于活动的蛋白质谱分析来鉴定特征不清的丝氨酸水解酶PLA2G4E作为小鼠脑Ca-NAT，并显示该酶在哺乳动物细胞中产生NAPE和NAE。

  DOI：

  10.1038/nchembio.2127

文献信息

• Discovery and Characterization of a Ca2+-independent Phosphatidylethanolamine N-Acyltransferase Generating the Anandamide Precursor and Its Congeners
  作者：Xing-Hua Jin、Yasuo Okamoto、Jun Morishita、Kazuhito Tsuboi、Takeharu Tonai、Natsuo Ueda

  DOI：10.1074/jbc.m606369200

  日期：2007.2

  N-Acylphosphatidylethanolamines (NAPEs) are precursors of bioactive N-acylethanolamines, including the endocannabinoid anandamide. In animal tissues, NAPE is formed by transfer of a fatty acyl chain at the sn-1 position of glycerophospholipids to the amino group of phosphatidylethanolamine (PE), and this reaction is believed to be the principal rate-limiting step in N-acylethanolamine synthesis. However, the Ca2+-dependent, membrane-associated N-acyltransferase (NAT) responsible for this reaction has not yet been cloned. In this study, on the basis of the functional similarity of NAT to lecithin-retinol acyltransferase (LRAT), we examined a possible PE N-acylation activity in two rat LRAT homologous proteins. Upon overexpression in COS-7 cells, one protein, named rat LRAT-like protein (RLP)-1, catalyzed transfer of a radioactive acyl group from phosphatidylicholine (PC) to PE, resulting in the formation of radioactive NAPE. However, the RLP-1 activity was detected mainly in the cytosolic rather than membrane fraction and was little stimulated by Ca2+. Moreover, RLP-1 did not show selectivity with respect to the sn-1 and sn-2 positions of PC as an acyl donor and therefore could generate N-arachidonoyl-PE (anandamide precursor) from 2-arachidonoyl-PC and PE. In contrast, under the same assay conditions, partially purified NAT from rat brain was highly Ca2+-dependent, membrane-associated, and specific for the sn-1-acyl group of PC. RLP-1 mRNA was expressed predominantly in testis among various rat tissues, and the testis cytosol exhibited an RLP-1-like activity. These results reveal that RLP-1 can function as a PE N-acyltransferase, catalytically distinguishable from the known Ca2+-dependent NAT.
• Molecular Characterization of a Phospholipase D Generating Anandamide and Its Congeners
  作者：Yasuo Okamoto、Jun Morishita、Kazuhito Tsuboi、Takeharu Tonai、Natsuo Ueda

  DOI：10.1074/jbc.m306642200

  日期：2004.2

  Anandamide (N-arachidonoylethanolamine) is known to be an endogenous ligand of cannabinoid and vanilloid receptors. Its congeners (collectively referred to as N-acylethanolamines) also show a variety of biological activities. These compounds are principally formed from their corresponding N-acyl-phosphatidylethanolamines by a phosphodiesterase of the phospholipase D-type in animal tissues. We purified the enzyme from rat heart, and by the use of the sequences of its internal peptides cloned its complementary DNAs from mouse, rat, and human. The deduced amino acid sequences were composed of 393-396 residues, and showed that the enzyme has no homology with the known phospholipase D enzymes but is classified as a member of the zinc metallohydrolase family of the beta-lactamase fold. As was overexpressed in COS-7 cells, the recombinant enzyme generated anandamide and other N-acylethanolamines from their corresponding N-acyl-phosphatidylethanolamines at comparable rates. In contrast, the enzyme was inactive with phosphatidylcholine and phosphatidylethanolamine. Assays of the enzyme activity and the messenger RNA and protein levels revealed its wide distribution in murine organs with higher contents in the brain, kidney, and testis. These results confirm that a specific phospholipase D is responsible for the generation of N-acylethanolamines including anandamide, strongly suggesting the physiological importance of lipid molecules of this class.
• The stimulatory effect of phosphatidylethanolamine on N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD)
  作者：Jun Wang、Yasuo Okamoto、Kazuhito Tsuboi、Natsuo Ueda

  DOI：10.1016/j.neuropharm.2007.06.001

  日期：2008.1

  N-Acylphosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD) is a membrane-bound enzyme which releases the endocannabinoid anandamide and other bioactive N-acylethanolamines from their corresponding NAPEs in animal tissues. Our previous studies showed that NAPE-PLD solubilized from the membrane is remarkably stimulated by millimolar concentrations of Ca2+ while the membrame- bound form is much less sensitive to Ca2+. This finding suggested that certain membrane constituents diminished the stimulatory effect of Ca2+. In the present studies, we examined the effects of membrane fractions from COS-7 cells and brain tissue on the purified recombinant rat NAPE-PLD. and found that heat-stable membrane component(s) dose-dependently activated NAPE-PLD up to 4.8-5.0 fold. In the presence of the membrane fractions, however, the stimulatory effect of Ca2+ on the purified NAPE-PLD was considerably reduced. When it was examined if the membrane fractions can be replaced with various pure phospholipids, phosphatidylethanolamine activated NAPE-PLD up to 3.3 fold, which was followed by decrease in the stimulatory effects of Ca2+ and several other divalent cations. These results suggest that membrane components including phosphatidylethanolamine keep the membrane-associated form of NAPE-PLD constitutively active. (c) 2007 Elsevier Ltd. All rights reserved.