5S,15S-dihydroperoxyeicosatetraenoic 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: 5S,15S-dihydroperoxyeicosatetraenoic acid
• 英文别名: 5,15-diHpETE；5S,15S-diHPETE；(5S,6E,8Z,11Z,13E,15S)-5,15-dihydroperoxyicosa-6,8,11,13-tetraenoic acid
• 化学式: C₂₀H₃₂O₆
• 分子量: 368.47
• InChiKey: PCIOUQYHTPPZEM-BVHTXILBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  花生四烯酸 在 leukocyte 5-lipoxygenase 作用下， 反应 2.0h， 生成 5S,15S-dihydroperoxyeicosatetraenoic acid
  参考文献：
  名称：

  5S,15S-Dihydroperoxyeicosatetraenoic Acid (5,15-diHpETE) as a Lipoxin Intermediate: Reactivity and Kinetics with Human Leukocyte 5-Lipoxygenase, Platelet 12-Lipoxygenase, and Reticulocyte 15-Lipoxygenase-1

  摘要：

  研究了5S,15S-二羟基过氧化二十碳四烯酸（5,15-diHpETE）与人类5-脂氧合酶（LOX）、人类血小板12-LOX和人类网织红细胞15-LOX-1的反应，以确定其反应性和生成脂氧素（LXs）的相对速度。5-LOX与5,15-diHpETE没有反应，尽管当15-HpETE作为底物时，它可以生成LXA4。相比之下，12-LOX和15-LOX-1均与5,15-diHpETE发生反应，特异性生成LXB4。对于12-LOX和5,15-diHpETE，其动力学参数为kcat = 0.17 s–1和kcat/KM = 0.011 μM–1 s–1（分别比12-LOX对花生四烯酸（AA）氧化的参数低106和1600倍）。另一方面，对于15-LOX-1，相应的参数为kcat = 4.6 s–1和kcat/KM = 0.21 μM–1 s–1（比15-LOX-1从AA生成12-HpETE高3倍且相似）。这与15-LOX-2与5,15-diHpETE完全没有反应形成对比[Green, A. R., et al. (2016) Biochemistry 55, 2832–2840]。我们的数据表明，12-LOX在催化5,15-diHpETE生成LXB4方面明显低于15-LOX-1。5,15-diHpETE的加入抑制了血小板聚集，IC50为1.3 μM；然而，LXB4在高达10 μM时对胶原介导的血小板活化没有显著抑制作用。总之，当5,15-diHpETE为底物时，LXB4是12-LOX和15-LOX-1催化的主要产物，且15-LOX-1的效率是12-LOX的20倍。5-LOX的主要产物是LXA4，但仅当15-HpETE为底物时。12-LOX生成的LXA4和LXB4大致成等比例，仅当LTA4为底物时，如之前所述[Sheppard, K. A., et al. (1992) Biochim. Biophys. Acta 1133, 223–234]。

  DOI：

  10.1021/acs.biochem.8b00889

文献信息

• 5<i>S</i>,15<i>S</i>-Dihydroperoxyeicosatetraenoic Acid (5,15-diHpETE) as a Lipoxin Intermediate: Reactivity and Kinetics with Human Leukocyte 5-Lipoxygenase, Platelet 12-Lipoxygenase, and Reticulocyte 15-Lipoxygenase-1
  作者：Abigail R. Green、Cody Freedman、Jennyfer Tena、Benjamin E. Tourdot、Benjamin Liu、Michael Holinstat、Theodore R. Holman

  DOI：10.1021/acs.biochem.8b00889

  日期：2018.12.4

  The reaction of 5S,15S-dihydroperoxyeicosatetraenoic acid (5,15-diHpETE) with human 5-lipoxygenase (LOX), human platelet 12-LOX, and human reticulocyte 15-LOX-1 was investigated to determine the reactivity and relative rates of producing lipoxins (LXs). 5-LOX does not react with 5,15-diHpETE, although it can produce LXA4 when 15-HpETE is the substrate. In contrast, both 12-LOX and 15-LOX-1 react with 5,15-diHpETE, forming specifically LXB4. For 12-LOX and 5,15-diHpETE, the kinetic parameters are kcat = 0.17 s–1 and kcat/KM = 0.011 μM–1 s–1 [106- and 1600-fold lower than those for 12-LOX oxygenation of arachidonic acid (AA), respectively]. On the other hand, for 15-LOX-1 the equivalent parameters are kcat = 4.6 s–1 and kcat/KM = 0.21 μM–1 s–1 (3-fold higher and similar to those for 12-HpETE formation by 15-LOX-1 from AA, respectively). This contrasts with the complete lack of reaction of 15-LOX-2 with 5,15-diHpETE [Green, A. R., et al. (2016) Biochemistry 55, 2832–2840]. Our data indicate that 12-LOX is markedly inferior to 15-LOX-1 in catalyzing the production of LXB4 from 5,15-diHpETE. Platelet aggregation was inhibited by the addition of 5,15-diHpETE, with an IC50 of 1.3 μM; however, LXB4 did not significantly inhibit collagen-mediated platelet activation up to 10 μM. In summary, LXB4 is the primary product of 12-LOX and 15-LOX-1 catalysis, if 5,15-diHpETE is the substrate, with 15-LOX-1 being 20-fold more efficient than 12-LOX. LXA4 is the primary product with 5-LOX but only if 15-HpETE is the substrate. Approximately equal proportions of LXA4 and LXB4 are produced by 12-LOX but only if LTA4 is the substrate, as described previously [Sheppard, K. A., et al. (1992) Biochim. Biophys. Acta 1133, 223–234].

  研究了5S,15S-二羟基过氧化二十碳四烯酸（5,15-diHpETE）与人类5-脂氧合酶（LOX）、人类血小板12-LOX和人类网织红细胞15-LOX-1的反应，以确定其反应性和生成脂氧素（LXs）的相对速度。5-LOX与5,15-diHpETE没有反应，尽管当15-HpETE作为底物时，它可以生成LXA4。相比之下，12-LOX和15-LOX-1均与5,15-diHpETE发生反应，特异性生成LXB4。对于12-LOX和5,15-diHpETE，其动力学参数为kcat = 0.17 s–1和kcat/KM = 0.011 μM–1 s–1（分别比12-LOX对花生四烯酸（AA）氧化的参数低106和1600倍）。另一方面，对于15-LOX-1，相应的参数为kcat = 4.6 s–1和kcat/KM = 0.21 μM–1 s–1（比15-LOX-1从AA生成12-HpETE高3倍且相似）。这与15-LOX-2与5,15-diHpETE完全没有反应形成对比[Green, A. R., et al. (2016) Biochemistry 55, 2832–2840]。我们的数据表明，12-LOX在催化5,15-diHpETE生成LXB4方面明显低于15-LOX-1。5,15-diHpETE的加入抑制了血小板聚集，IC50为1.3 μM；然而，LXB4在高达10 μM时对胶原介导的血小板活化没有显著抑制作用。总之，当5,15-diHpETE为底物时，LXB4是12-LOX和15-LOX-1催化的主要产物，且15-LOX-1的效率是12-LOX的20倍。5-LOX的主要产物是LXA4，但仅当15-HpETE为底物时。12-LOX生成的LXA4和LXB4大致成等比例，仅当LTA4为底物时，如之前所述[Sheppard, K. A., et al. (1992) Biochim. Biophys. Acta 1133, 223–234]。