19-hydroxyeicosatetraenoic acid | 79551-85-2

• 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: 19-hydroxyeicosatetraenoic acid
• 英文别名: 19-HETE；19-Hydroxyarachidonic acid；(5Z,8Z,11Z,14Z)-19-hydroxyicosa-5,8,11,14-tetraenoic acid
• CAS: 79551-85-2
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: XFUXZHQUWPFWPR-TWVHMNNTSA-N

物化性质

• 沸点：
  477.3±45.0 °C(Predicted)
• 密度：
  0.984±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

19-HETE是花生四烯酸的一种已知人类代谢物。

19-HETE is a known human metabolite of arachidonic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  19-hydroxyeicosatetraenoic acid 在 吡啶 、 sodium azide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (5Z,8Z,11Z,14Z)-19-azidoeicosa-5,8,11,14-tetraenoic acid
  参考文献：
  名称：

  Synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-3H8]-analogues through a common synthetic route

  摘要：

  Total synthesis of (5Z,8Z, 11Z, 14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-H-3(8)]-analogues via the corresponding p-toluenesulphonates is reported. This synthetic approach allows the preparation of radioactively labelled arachidonic acid derivatives following a common synthetic route. Activity assays indicated that 15-lipoxygenases may tolerate the azido group in the substrate binding pocket and thus, radioactively labelled azido compounds may be used as photo-affinity probes to investigate mechanistic features of eicosanoid biosynthesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.chemphyslip.2004.02.008
• 作为产物：
  描述：

  花生四烯酸 生成 19-hydroxyeicosatetraenoic acid
  参考文献：
  名称：

  氧化前列腺素E的一般生物化学合成。

  摘要：

  DOI：

  10.1021/ja01041a065

文献信息

• Endocannabinoids Anandamide and 2-Arachidonoylglycerol Are Substrates for Human CYP2J2 Epoxygenase
  作者：Daniel R. McDougle、Amogh Kambalyal、Daryl D. Meling、Aditi Das

  DOI：10.1124/jpet.114.216598

  日期：2014.12

  The endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are arachidonic acid (AA) derivatives that are known to regulate human cardiovascular functions. CYP2J2 is the primary cytochrome P450 in the human heart and is most well known for the metabolism of AA to the biologically active epoxyeicosatrienoic acids. In this study, we demonstrate that both 2-AG and AEA are substrates for metabolism by CYP2J2 epoxygenase in the model membrane bilayers of nanodiscs. Reactions of CYP2J2 with AEA formed four AEA-epoxyeicosatrienoic acids, whereas incubations with 2-AG yielded detectable levels of only two 2-AG epoxides. Notably, 2-AG was shown to undergo enzymatic oxidative cleavage to form AA through a NADPH-dependent reaction with CYP2J2 and cytochrome P450 reductase. The formation of the predominant AEA and 2-AG epoxides was confirmed using microsomes prepared from the left myocardium of porcine and bovine heart tissues. The nuances of the ligand-protein interactions were further characterized using spectral titrations, stopped-flow small-molecule ligand egress, and molecular modeling. The experimental and theoretical data were in agreement, which showed that substitution of the AA carboxylic acid with the 2-AG ester-glycerol changes the binding interaction of these lipids within the CYP2J2 active site, leading to different product distributions. In summary, we present data for the functional metabolomics of AEA and 2-AG by a membrane-bound cardiovascular epoxygenase.

  内源性大麻素，阿南达胺（AEA）和2-花生四烯酸甘油酯（2-AG），是已知能调节人类心血管功能的花生四烯酸（AA）衍生物。CYP2J2是人类心脏中的主要细胞色素P450，最为人知的是将AA代谢为生物活性环氧二十烯酸。在本研究中，我们表明2-AG和AEA都是CYP2J2环氧化酶在纳米盘膜模型中代谢的底物。CYP2J2与AEA的反应形成了四种AEA-环氧二十烯酸，而与2-AG的孵育仅产生可检测到的两种2-AG环氧化物。值得注意的是，2-AG在CYP2J2和细胞色素P450还原酶的NADPH依赖反应下，显示出经历酶促氧化裂解，形成AA。通过使用从猪和牛心脏左心肌样本制备的微粒体，确认了主要AEA和2-AG环氧化物的形成。我们进一步通过光谱滴定、停止流小分子配体逸出和分子建模来表征配体-蛋白质相互作用的细微差别。实验和理论数据一致，表明用2-AG酯甘油替代AA羧酸改变了这些脂质在CYP2J2活性位点内的结合相互作用，从而导致不同的产物分布。总之，我们提供了关于膜结合的心血管环氧化酶对AEA和2-AG的功能代谢组学的数据。
• Repurposing Resveratrol and Fluconazole To Modulate Human Cytochrome P450-Mediated Arachidonic Acid Metabolism
  作者：Ahmed A. El-Sherbeni、Ayman O. S. El-Kadi

  DOI：10.1021/acs.molpharmaceut.5b00873

  日期：2016.4.4

  Cytochrome P450 (P450) enzymes metabolize arachidonic acid (AA) to several biologically active epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Repurposing clinically-approved drugs could provide safe and readily available means to control EETs and HETEs levels in humans. Our aim was to determine how to significantly and selectively modulate P450-AA metabolism in humans by

  细胞色素P450（P450）酶将花生四烯酸（AA）代谢为几种具有生物活性的环氧二十碳三烯酸（EET）和羟基二十碳四烯酸（HETE）。重新使用经过临床批准的药物可以为控制人类中的EET和HETE水平提供安全且容易获得的手段。我们的目标是确定如何通过临床批准的药物显着和选择性地调节人体内的P450-AA代谢。液相色谱-质谱法用于测定人重组P450酶以及人肝和肾微粒体形成的15种AA代谢产物。CYP2C19显示最高的EET形成活性，而CYP1B1和CYP2C8显示最高的中链HETE形成活性。CYP1A1和CYP4分别显示出最高的亚末端和20-HETE形成活性。与研究药物相比，白藜芦醇和氟康唑对肝P450-AA代谢产生了最有选择性和最显着的调节作用。蒙特卡洛模拟显示，每天服用2.5克后，有90％的人口在16-，18-和20-HETE形成中分别减少6-22％，16-39％和16-35％。白藜芦醇，氟康唑50
• Synthesis of arachidonic acid metabolites produced by purified kidney cortex microsomal cytochrome P-450
  作者：Sukamar Manna、J.R. Falck、N. Chacos、J. Capdevila

  DOI：10.1016/s0040-4039(00)81319-2

  日期：1983.1
• Pseudomonas aeruginosa cytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE
  作者：Brian C. Tooker、Sylvie E. Kandel、Hannah M. Work、Jed N. Lampe

  DOI：10.1016/j.jbc.2022.101629

  日期：2022.3
• TREATMENT OF A DISEASE MEDIATED BY ARACHIDONIC ACID OR AN EICOSANOID
  申请人：GADAMIAN Robert

  公开号：US20190231730A1

  公开（公告）日：2019-08-01

  Disclosed is a method of treating a disease mediated by arachidonic acid or an eicosanoid. The method includes administering to a subject in need thereof an effective amount of an analogue of arachidonic acid or an analogue of eicosanoid. The analogue is a dehydro-analogue of an arachidonic acid, HPETE, EET, a prostaglandin or HETE. Diseases that may be treated include cancer, ischemic heart disease, psoriasis, cystic fibrosis, Alzheimer's disease, allergy, COPD, rheumatoid arthritis (RA), ulcerative colitis, or Crohn's disease.