leukotriene A4

• 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: leukotriene A4
• 英文别名: LTA4；4-[(2S,3S)-3-tetradeca-1,3,5,8-tetraenyloxiran-2-yl]butanoic acid
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: UFPQIRYSPUYQHK-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  leukotriene A4 在 LTA₄H 作用下， 生成 白三烯B4
  参考文献：
  名称：

  COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes

  摘要：

  Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-di-HETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5S-HETE as a substrate for COX-2 forming 5S,15S-diHETE, 5S,15R-diHETE, and 5S,11R-di-HETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 +/- 0.2 ng/10(6) cells (mean +/- SEM, n = 6), reaching about half the level of LTB(4) (1.3 +/- 0.5 ng/10(6) cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/10(6) cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 +/- 0.05 ng/10(6) cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5S,12S-diHETE with the unusual 6E,8Z,10E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A(4)-epoxide. Exogenous octadeuterated 5S-HETE and 15S-HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5-LOX in activated human leukocytes.-Tejera, N., W. E. Boeglin, T. Suzuki, and C. Schneider. COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. J. Lipid Res. 2012. 53: 87-94.

  DOI：

  10.1194/jlr.m017822
• 作为产物：
  描述：

  花生四烯酸 在 脂肪氧化酶 作用下， 生成 leukotriene A4
  参考文献：
  名称：

  COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes

  摘要：

  Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-di-HETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5S-HETE as a substrate for COX-2 forming 5S,15S-diHETE, 5S,15R-diHETE, and 5S,11R-di-HETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 +/- 0.2 ng/10(6) cells (mean +/- SEM, n = 6), reaching about half the level of LTB(4) (1.3 +/- 0.5 ng/10(6) cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/10(6) cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 +/- 0.05 ng/10(6) cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5S,12S-diHETE with the unusual 6E,8Z,10E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A(4)-epoxide. Exogenous octadeuterated 5S-HETE and 15S-HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5-LOX in activated human leukocytes.-Tejera, N., W. E. Boeglin, T. Suzuki, and C. Schneider. COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. J. Lipid Res. 2012. 53: 87-94.

  DOI：

  10.1194/jlr.m017822

文献信息

• Metabolomics-Based Identification of Disease-Causing Agents
  申请人：Skolnick Jeffrey

  公开号：US20110246081A1

  公开（公告）日：2011-10-06

  A method, computer-readable medium, and system for identifying one or more metabolites associated with a disease, comprising: comparing gene expression data from diseased cells to gene expression data from control cells in order to deduce genes that are differentially-regulated in the diseased cells relative to the control cells; based on enzyme function and pathway data for all human metabolites that utilize the genes that are differentially-regulated in the disease cells, identifying one or more metabolites whose intracellular levels are higher or lower in diseased cells than in control cells, and thereby associating the one or more metabolites with the disease.
• COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes
  作者：Noemi Tejera、William E. Boeglin、Takashi Suzuki、Claus Schneider

  DOI：10.1194/jlr.m017822

  日期：2012.1

  Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-di-HETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5S-HETE as a substrate for COX-2 forming 5S,15S-diHETE, 5S,15R-diHETE, and 5S,11R-di-HETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 +/- 0.2 ng/10(6) cells (mean +/- SEM, n = 6), reaching about half the level of LTB(4) (1.3 +/- 0.5 ng/10(6) cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/10(6) cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 +/- 0.05 ng/10(6) cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5S,12S-diHETE with the unusual 6E,8Z,10E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A(4)-epoxide. Exogenous octadeuterated 5S-HETE and 15S-HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5-LOX in activated human leukocytes.-Tejera, N., W. E. Boeglin, T. Suzuki, and C. Schneider. COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. J. Lipid Res. 2012. 53: 87-94.