N,1-dipalmitoyl-2-linoleoyl-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-dipalmitoyl-2-linoleoyl-sn-glycero-3-phosphoethanolamine(1-)
• 英文别名: 2-(hexadecanoylamino)ethyl [(2R)-3-hexadecanoyloxy-2-[(9Z,12Z)-octadeca-9,12-dienoyl]oxypropyl] phosphate
• 化学式: C55H103NO9P-
• 分子量: 953.4
• InChiKey: FYGZHQXBEOHSAS-WGAYFDSDSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  19.5
• 重原子数：
  66
• 可旋转键数：
  54
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 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-dipalmitoyl-2-linoleoyl-sn-glycero-3-phosphoethanolamine(1-) 生成 1-16:0-2-18:2-Phosphatidate 、 氢(+1)阳离子 、 十六酰胺乙醇
  参考文献：
  名称：

  Molecular Characterization of a Phospholipase D Generating Anandamide and Its Congeners

  摘要：

  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.

  DOI：

  10.1074/jbc.m306642200

文献信息

• Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D
  作者：Yong-Xin SUN、Kazuhito TSUBOI、Yasuo OKAMOTO、Takeharu TONAI、Makoto MURAKAMI、Ichiro KUDO、Natsuo UEDA

  DOI：10.1042/bj20040031

  日期：2004.6.15

  Anandamide (an endocannabinoid) and other bioactive long-chain NAEs (N-acylethanolamines) are formed by direct release from N-acyl-PE (N-acyl-phosphatidylethanolamine) by a PLD (phospholipase D). However, the possible presence of a two-step pathway from N-acyl-PE has also been suggested previously, which comprises (1) the hydrolysis of N-acyl-PE to N-acyl-lysoPE by PLA1/PLA2 enzyme(s) and (2) the release of NAEs from N-acyllysoPE by lysoPLD (lysophospholipase D) enzyme(s). In the present study we report for the first time the characterization of enzymes responsible for this pathway. The PLA1/PLA2 activity for N-palmitoyl-PE was found in various rat tissues, with the highest activity in the stomach. This stomach enzyme was identified as group IB sPLA2 (secretory PLA2), and its product was determined as N-acyl-1-acyl-lysoPE. Recombinant group IB, IIA and V of sPLA2s were also active with N-palmitoyl-PE, whereas group X sPLA2 and cytosolic PLA2α were inactive. In addition, we found wide distribution of lysoPLD activity generating N-palmitoylethanolamine from N-palmitoyl-lysoPE in rat tissues, with higher activities in the brain and testis. Based on several lines of enzymological evidence, the lysoPLD enzyme could be distinct from the known N-acyl-PE-hydrolysing PLD. sPLA2-IB dose dependently enhanced the production of N-palmitoylethanolamine from N-palmitoyl-PE in the brain homogenate showing the lysoPLD activity. N-Arachidonoyl-PE and N-arachidonoyl-lysoPE as anandamide precursors were also good substrates of sPLA2-IB and the lysoPLD respectively. These results suggest that the sequential actions of PLA2 and lysoPLD may constitute another biosynthetic pathway for NAEs, including anandamide.

  安乃近（一种内源性大麻素）和其他具有生物活性的长链 NAE（N-酰乙醇胺）是由 PLD（磷脂酶 D）从 N-酰-PE（N-酰基磷脂酰乙醇胺）中直接释放出来的。不过，以前也有人提出过 N-酰基-PE可能存在两步途径，其中包括：(1) N-酰基-PE通过 PLA1/PLA2 酶水解为 N-酰基-lysoPE；(2) N-酰基-lysoPE通过溶血磷脂酶 D（lysoPLD）酶释放出 NAE。在本研究中，我们首次报告了负责这一途径的酶的特征。在大鼠的多种组织中发现了 N-棕榈酰-PE 的 PLA1/PLA2 活性，其中胃中的活性最高。这种胃酶被鉴定为 IB 组 sPLA2（分泌型 PLA2），其产物被确定为 N-酰基-1-酰基-lysoPE。重组的 IB、IIA 和 V 组 sPLA2 对 N-棕榈酰-PE 也有活性，而 X 组 sPLA2 和细胞质 PLA2α 则没有活性。此外，我们还发现从 N-棕榈酰-lysoPE生成 N-棕榈酰乙醇胺的溶菌 PLD 活性在大鼠组织中分布广泛，其中大脑和睾丸中的活性较高。sPLA2-IB 的剂量依赖性增强了显示溶菌酶活性的脑匀浆中 N-棕榈酰-PE 生成 N-棕榈酰乙醇胺的能力。N- arachidonoyl-PE 和 N- arachidonoyl-lysoPE 作为安乃近前体也分别是 sPLA2-IB 和 lysoPLD 的良好底物。这些结果表明，PLA2 和 lysoPLD 的相继作用可能构成包括安乃近酰胺在内的 NAEs 的另一种生物合成途径。