5(S)-Hydroperoxy-6,8,11,14-eicosatetraenoic 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: 5(S)-Hydroperoxy-6,8,11,14-eicosatetraenoic acid
• 英文别名: 5S-hydroperoxyeicosatetraenoic acid；5S-HPETE；(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoic acid
• 化学式: C₂₀H₃₂O₄
• 分子量: 336.472
• InChiKey: JNUUNUQHXIOFDA-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5(S)-Hydroperoxy-6,8,11,14-eicosatetraenoic acid 在 脂肪氧化酶 、 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 5(S)-Hydroperoxy-6,8,11,14-eicosatetraenoic acid
  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

• 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.