12-hydroxyeicosatetraenoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 12-hydroxyeicosatetraenoic acid
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: ZNHVWPKMFKADKW-QGXLQBIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.19
• 重原子数：
  23.0
• 可旋转键数：
  14.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  在 human carboxylesterase 1 、 水 作用下， 以 甲醇 为溶剂， 生成 12-hydroxyeicosatetraenoic acid 、 花生四烯酸
  参考文献：
  名称：

  CES1 从氧化三酰甘油 (oxTAG) 中释放氧脂质并调节巨噬细胞 oxTAG/TAG 积累和 PGE2/IL-1β 产生

  摘要：

  三酰甘油（TAG）是脂肪的储存形式，主要存在于细胞的细胞质脂滴中。当需要燃料储备时，TAG 被脂肪分解酶分解为其成分游离脂肪酸。然而，含有多不饱和脂肪酸 (PUFA) 的 TAG 容易发生非酶氧化反应，导致形成与甘油主链酯化的氧脂质 (称为 oxTAG)。人羧酸酯酶 1 (CES1) 是丝氨酸水解酶超家族的成员，因其催化有毒物质和脂质中的羧基酯键水解的能力而被定义。 CES1是一种真正的TAG水解酶，但尚不清楚在脂肪分解过程中优先释放哪些特定脂肪酸。为了更好地了解 CES1 在巨噬细胞等免疫细胞中的生化功能，需要研究其在 TAG 脂滴中遇到氧化 PUFA 时的底物选择性。我们试图鉴定 CES1 从 oxTAG 中释放的那些酯化氧化脂肪酸，因为它们的释放可以激活信号通路，从而促进脂质驱动炎症的发展。获得这些知识将有助于填补 CES1 与脂质敏感核受体 PPARγ 和 LXRα 之间存在的数据

  DOI：

  10.1021/acschembio.3c00194

文献信息

• Identification of an amino acid determinant of pH regiospecificity in a seed lipoxygenase from Momordica charantia
  作者：Ellen Hornung、Susan Kunze、Alena Liavonchanka、Grit Zimmermann、Diana Kühn、Kathrin Fritsche、Andreas Renz、Hartmut Kühn、Ivo Feussner

  DOI：10.1016/j.phytochem.2008.09.006

  日期：2008.11

  Lipoxygenases (LOX) form a heterogeneous family of lipid peroxidizing enzymes, which catalyze specific dioxygenation of polyunsaturated fatty acids. According to their positional specificity of linoleic acid oxygenation plant LOX have been classified into linoleate 9- and linoleate 13-LOX and recent reports identified a critical valine at the active site of 9-LOX. In contrast, more bulky phenylalanine or histidine residues were found at this position in 13-LOX. We have recently cloned a LOX-isoform from Momordica charantia and multiple amino acid alignments indicated the existence of a glutamine (Gln599) at the position were 13-LOX usually carry histidine or phenylalanine residues. Analyzing the pH-dependence of the positional specificity of linoleic acid oxygenation we observed that at pH-values higher than 7.5 this enzyme constitutes a linoleate 13-LOX whereas at lower pH, 9-H(P)ODE was the major reaction product. Site-directed mutagenesis of glutamine 599 to histidine (Gln599His) converted the enzyme to a pure 13-LOX. These data confirm previous observation suggesting that reaction specificity of certain LOX-isoforms is not an absolute enzyme property but may be impacted by reaction conditions such as pH of the reaction mixture. We extended this concept by identifying glutamine 599 as sequence determinant for such pH-dependence of the reaction specificity. Although the biological relevance for this alteration switch remains to be investigated it is of particular interest that it occurs at near physiological conditions in the pH-range between 7 and 8. (C) 2008 Elsevier Ltd. All rights reserved.
• ω-Alkynyl Lipid Surrogates for Polyunsaturated Fatty Acids: Free Radical and Enzymatic Oxidations
  作者：William N. Beavers、Remigiusz Serwa、Yuki Shimozu、Keri A. Tallman、Melissa Vaught、Esha D. Dalvie、Lawrence J. Marnett、Ned A. Porter

  DOI：10.1021/ja506038v

  日期：2014.8.13

  Lipid and lipid metabolite profiling are important parameters in understanding the pathogenesis of many diseases. Alkynylated polyunsaturated fatty acids are potentially useful probes for tracking the fate of fatty acid metabolites. The nonenzymatic and enzymatic oxidations of omega-alkynyl linoleic acid and omega-alkynyl arachidonic acid were compared to that of linoleic and arachidonic acid. There was no detectable difference in the primary products of nonenzymatic oxidation, which comprised cis,trans-hydroxy fatty acids. Similar hydroxy fatty acid products were formed when omega-alkynyl linoleic acid and omega-alkynyl arachidonic acid were reacted with lipoxygenase enzymes that introduce oxygen at different positions in the carbon chains. The rates of oxidation of omega-alkynylated fatty acids were reduced compared to those of the natural fatty acids. Cyclooxygenase-1 and -2 did not oxidize alkynyl linoleic but efficiently oxidized alkynyl arachidonic acid. The products were identified as alkynyl 11-hydroxy-eicosatetraenoic acid, alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid, and alkynyl prostaglandins. This deviation from the metabolic profile of arachidonic acid may limit the utility of alkynyl arachidonic acid in the tracking of cyclooxygenase-based lipid oxidation. The formation of alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid compared to alkynyl prostaglandins suggests that the omega-alkyne group causes a conformational change in the fatty acid bound to the enzyme, which reduces the efficiency of cyclization of dioxalanyl intermediates to endoperoxide intermediates. Overall, omega-alkynyl linoleic acid and omega-alkynyl arachidonic acid appear to be metabolically competent surrogates for tracking the fate of polyunsaturated fatty acids when looking at models involving autoxidation and oxidation by lipoxygenases.