PC(0:0/20:4(5Z,8Z,11Z,14Z)) | 67341-29-1

• 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: PC(0:0/20:4(5Z,8Z,11Z,14Z))
• 英文别名: [(2R)-3-hydroxy-2-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate
• CAS: 67341-29-1
• 化学式: C28H50NO7P
• 分子量: 543.7
• InChiKey: IGJKYDBBINVMLH-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：

  PC(0:0/20:4(5Z,8Z,11Z,14Z)) 生成 二花生四烯酰基-L-alpha-卵磷脂 、 甘磷酸胆碱
  参考文献：
  名称：

  大鼠肝脏60-kDa溶血磷脂酶-转酰酶的转酰酶活性的表征。酰基从sn-2转移到sn-1位置。

  摘要：

  大鼠肝脏60 kDa溶血磷脂酶-转酰酶不仅催化1-酰基-sn-甘油-3-磷酸胆碱的水解，而且还将其酰基链转移到1-酰基-sn-甘油-3-磷酸胆碱的第二个分子上形成磷脂酰胆碱（H.Sugimoto，S.Yamashita，J.Biol.Chem.269（1994）6252-6258）。在这里，我们报告该酶的转酰酶活性的详细特征。该酶介导了供体脂质和受体脂质之间的三种类型的酰基转移，将酰基残基从以下位置转移：（1）sn-1至-1（3）；（2）sn-1至-2; （3）sn-2至-1位置。在从sn-1到-1（3）的转移过程中，1-酰基-sn-甘油-3-磷酸胆碱的sn-1酰基残基转移到了甘油和2-酰基-sn的sn-1（3）位置-甘油，分别产生1（3）-酰基-sn-甘油和1,2-二酰基-sn-甘油。在从sn-1到-2的传输中，1-酰基-sn-甘油-3-磷酸胆碱的sn-1酰基残基不仅转移到1-酰基-sn

  DOI：

  10.1016/s1388-1981(99)00059-1
• 作为产物：
  描述：

  2-花生四烯酰-1-棕榈酰-sn-甘油-3-磷酸胆碱 、 N-乙酰基神经鞘氨醇 生成 1-O-palmitoyl-N-acetylsphingosine 、 PC(0:0/20:4(5Z,8Z,11Z,14Z))
  参考文献：
  名称：

  溶酶体磷脂酶A2的位置特异性。

  摘要：

  溶酶体磷脂酶A（2）（Lpla2）在肺泡巨噬细胞中高度表达，并可能介导表面活性剂的磷脂代谢。对这种磷脂酶特性的研究与磷脂酶A（1）和磷脂酶A（2）活性的存在是一致的。通过生产由Lpla2的转酰酶活性产生的O-酰基化合物来研究这些活性。将含有POPC和N-乙酰基鞘氨醇（NAS）的脂质体与从稳定转染了小鼠Lpla2基因的MDCK细胞获得的可溶性级分一起孵育。Lpla2生产了两个1-O-酰基-NAS，1-O-棕榈酰基-NAS和1-O-油酰基-NAS。1-O-油酰基-NAS的形成速率是1-O-棕榈酰基-NAS的2.5倍。当使用1-油酰基-2-棕榈酰基-sn-甘油-3-磷酸胆碱（OPPC）时，1-O-油酰基-NAS的形成速率是1-O-棕榈酰基-NAS的5倍。因此，Lpla2可以在POPC和OPPC的sn-1和sn-2位置同时作用于酰基。当使用1-棕榈酰基-2-不饱和酰基-sn-甘油-3-磷酸胆碱作为

  DOI：

  10.1194/jlr.m600183-jlr200

文献信息

• Determinants of pH profile and acyl chain selectivity in lysosomal phospholipase A2 [S]
  作者：Vania Hinkovska-Galcheva、Robert Kelly、Kelly A. Manthei、Renee Bouley、Wenmin Yuan、Anna Schwendeman、JohnJ.G. Tesmer、James A. Shayman

  DOI：10.1194/jlr.m084012

  日期：——

  Lysosomal phospholipase A2 (LPLA2) is characterized by broad substrate recognition, peak activity at acidic pH, and the transacylation of lipophilic alcohols, especially N-acetyl-sphingosine. Prior structural analysis of LPLA2 revealed the presence of an atypical acidic residue, Asp13, in the otherwise hydrophobic active site cleft. We hypothesized that Asp13 contributed to the pH profile and/or substrate

  溶酶体磷脂酶A2（LPLA2）的特征是广泛的底物识别，在酸性pH下具有峰值活性以及亲脂性醇（尤其是N-乙酰基-鞘氨醇）的酰基转移。LPLA2的先前结构分析显示，在否则为疏水活性位点的裂口中存在非典型酸性残基Asp13。我们假设Asp13有助于pH谱和/或LPLA2对不饱和酰基链的底物偏爱。为了验证这一假设，我们用Asp13取代了丙氨酸，半胱氨酸或苯丙氨酸。然后，我们监测了1-O-酰基-N-乙酰基鞘氨醇的形成，以测量各种甘油磷脂上sn-1和sn-2酰基的水解情况。在中性pH值下，用Asp13取代产生显着的酶活性（7。4）并干扰了单不饱和和双不饱和酰基链的选择性。但是，该位置在选择酰基受体或甘油磷脂的头基中没有明显作用。我们的模型表明，Asp13及其取代基通过形成易碎的酰基链所占据的疏水轨道的一部分，有助于LPLA2的pH活性曲线和酰基链选择性。
• Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids
  作者：Jonathan Z Long、Justin S Cisar、David Milliken、Sherry Niessen、Chu Wang、Sunia A Trauger、Gary Siuzdak、Benjamin F Cravatt

  DOI：10.1038/nchembio.659

  日期：2011.11

  An untargeted metabolomics approach identifies C14 phosphatidylcholines (PCs) as specific cellular medium-chain substrates of the lipase ABHD3, as well as C5–C8 short-chain PCs including oxidized pro-atherosclerotic and pro-apoptotic PC phospholipids. All organisms, including humans, possess a huge number of uncharacterized enzymes. Here we describe a general cell-based screen for enzyme substrate discovery by untargeted metabolomics and its application to identify the protein α/β-hydrolase domain–containing 3 (ABHD3) as a lipase that selectively cleaves medium-chain and oxidatively truncated phospholipids. Abhd3−/− mice possess elevated myristoyl (C14)-phospholipids, including the bioactive lipid C14-lysophosphatidylcholine, confirming the physiological relevance of our substrate assignments.

  一种非靶向代谢组学方法发现，C14磷脂酰胆碱（PC）是脂肪酶ABHD3的特异性细胞中链底物，还发现了C5âC8短链PC，包括氧化的促动脉粥样硬化和促凋亡PC磷脂。 包括人类在内的所有生物体都拥有大量未定性的酶。在这里，我们描述了一种通过非靶向代谢组学发现酶底物的通用细胞筛选方法，以及该方法在鉴定含δ/δ²-水解酶结构域的蛋白δ/δ²-水解酶结构域3（ABHD3）的应用，该蛋白δ/δ²-水解酶结构域3（ABHD3）是一种选择性裂解中链和氧化截短磷脂的脂肪酶。ABHD3â/â小鼠的肉豆蔻酰（C14）-磷脂含量升高，其中包括生物活性脂质C14-赖磷脂酰胆碱，这证实了我们底物分配的生理相关性。
• The phospholipase iPLA2γ is a major mediator releasing oxidized aliphatic chains from cardiolipin, integrating mitochondrial bioenergetics and signaling
  作者：Gao-Yuan Liu、Sung Ho Moon、Christopher M. Jenkins、Maoyin Li、Harold F. Sims、Shaoping Guan、Richard W. Gross

  DOI：10.1074/jbc.m117.783068

  日期：2017.6

  aliphatic chains from CL. Our results also indicated that iPLA2γ selectively hydrolyzes 9-hydroxy-octadecenoic acid in comparison to 13-hydroxy-octadecenoic acid from oxidized CLs. Moreover, oxidative stress (ADP, NADPH, and Fe3+) resulted in the robust production of oxidized CLs in intact mitochondria from iPLA2γ-/- mice. In sharp contrast, oxidized CLs were readily hydrolyzed in mitochondria from wild-type

  心磷脂（CL）是一种二聚体磷脂，在线粒体生物能和信号传导中起关键作用。最近，钙非依赖性磷脂酶A2γ（iPLA2γ）-选择性抑制剂（R）-BEL抑制了CL氧化脂肪酰基链的释放，表明iPLA2γ负责氧化的CL的水解以及随后由释放的氧化的OH介导的信号传导。脂肪酸。但是，BEL的化学抑制作用会偏离目标药理作用。因此，为了明确确定iPLA2γ在氧化的CL水解中的作用，我们在纯化的重组iPLA2γ，种系iPLA2γ-//小鼠，心肌细胞实验中比较了氧化CL的变化和CL中氧化脂肪族链的释放。特异性iPLA2γ转基因小鼠和野生型小鼠。使用带有选定反应监测和产物离子精确质量的电荷转换高质量精确度LC-MS / MS，我们证明iPLA2γ是负责从CL释放氧化的脂肪族链的主要酶。我们的结果还表明，与来自氧化CL的13-羟基-十八碳烯酸相比，iPLA2γ选择性水解9-羟基-十八碳烯酸。此外，氧化应激（ADP，NADPH和Fe3
• A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines
  作者：Yuji Ogura、William H Parsons、Siddhesh S Kamat、Benjamin F Cravatt

  DOI：10.1038/nchembio.2127

  日期：2016.9

  More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remained mysterious. Here, we use activity-based protein profiling to identify the poorly

  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。
• 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.