11-HETE | 71030-38-1

• 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: 11-HETE
• 英文别名: 11-hydroxyeicosatetraenoic acid；11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid；11-hydroxy-5Z,8Z,11E,14Z-eicosatetraenoic acid；(5Z,8Z,12E,14Z)-11-hydroxyicosa-5,8,12,14-tetraenoic acid
• CAS: 71030-38-1
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: GCZRCCHPLVMMJE-RLZWZWKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 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

11-羟基二十烷酸是人花生四烯酸的已知代谢物。

11-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：

  11-HETE 在 三苯基膦 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (5S,11S)-5,11-dihydroxy-eicosa-6,8,12,14-tetraenoic acid 、 (5S,11R)-5,11-dihydroxy-eicosa-6,8,12,14-tetraenoic acid 、 (5R,11S)-5,11-dihydroxy-eicosa-6,8,12,14-tetraenoic acid 、 (5R,11R)-5,11-dihydroxy-eicosa-6,8,12,14-tetraenoic acid
  参考文献：
  名称：

  Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2

  摘要：

  Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11R-hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5S-HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC-MS, and LC-MS analysis. 5S,15S- dihydroxy (di)HETE, 5S,15R-diHETE, and 5S,11R-diHETE were identified as by-products of native COX-2, in addition to the previously described di-endoperoxide (5S,15S-dihydroxy-9S,11R,8S,12S-diperoxy-6E,13E-eicosadienoic acid) as the major oxygenation product. 5S,15R-diHETE was the only product formed by aspirin-acetylated COX-2. Both 5,15-diHETE and 5,11-diHETE were detected in CT26 mouse colon carcinoma cells as well as in lipopolysaccharide-activated RAW264.7 cells incubated with 5S-HETE, and their formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398. Aspirin-treated CT26 cells gave 5,15-diHETE as the most prominent product formed from 5S-HETE. 5S,15S-diHETE has been described as a product of the cross-over of 5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells and human leukocytes, and our studies implicate crossover of the 5-LOX and COX-2 pathways as an additional bio-synthetic route.-Mulugeta, S., T. Suzuki, N. T. Hernandez, M. Griesser, W. E. Boeglin, and C. Schneider. Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2. J. Lipid Res. 2010. 51: 575-585.

  DOI：

  10.1194/jlr.m001719
• 作为产物：
  描述：

  cis-11,12-epoxyeicosatrienoic acid methyl ester 在 lithium hydroxide 、 N-环己基异丙基胺 、 甲基溴化镁 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 20.5h， 生成 11-HETE
  参考文献：
  名称：

  Controlled chemical synthesis of the enzymically produced eicosanoids 11-, 12-, and 15-HETE from arachidonic acid and conversion into the corresponding hydroperoxides (HPETE)

  摘要：

  DOI：

  10.1021/ja00524a043

文献信息

• 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
• Differential diagnosis of liver disease
  申请人：The Regents of the University of California

  公开号：US10422786B2

  公开（公告）日：2019-09-24

  The present invention relates to the substantially non-invasive diagnosis of liver disease, especially to enable intervention in the progression of such disease at an early stage. This invention further relates to the use of plasma biomarkers to differentiate nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver (NAFL) and non-nonalcoholic fatty liver disease (NAFLD), and normal controls. Specifically, the invention relates to the use of free eicosanoids and other polyunsaturated fatty acid (PUFA) metabolite levels in plasma to differentiate NASH from NAFL and non-NAFLD normal controls.

  本发明涉及肝脏疾病的基本无创诊断，特别是能够在早期阶段对此类疾病的进展进行干预。本发明进一步涉及使用血浆生物标志物来区分非酒精性脂肪性肝炎（NASH）与非酒精性脂肪肝（NAFL）和非酒精性脂肪肝（NAFLD）以及正常对照组。具体来说，本发明涉及利用血浆中游离二十烷酸和其他多不饱和脂肪酸（PUFA）代谢物水平来区分非酒精性脂肪性肝炎（NASH）和非酒精性脂肪性肝病（NAFL）以及非酒精性脂肪性肝病（NAFLD）正常对照组。
• Physcomitrella patens has lipoxygenases for both eicosanoid and octadecanoid pathways
  作者：Aldwin Anterola、Cornelia Göbel、Ellen Hornung、George Sellhorn、Ivo Feussner、Howard Grimes

  DOI：10.1016/j.phytochem.2008.11.012

  日期：2009.1

  Mosses have substantial amounts of long chain C20 polyunsaturated fatty acids, such as arachidonic and eicosapentaenoic acid, in addition to the shorter chain C18 alpha-linolenic and linoleic acids, which are typical substrates of lipoxygenases in flowering plants. To identify the fatty acid substrates used by moss lipoxygenases, eight lipoxygenase genes from Physcomitrella patens were heterologously expressed in Escherichia coli, and then analyzed for lipoxygenase activity using linoleic, alpha-linolenic and arachidonic acids as substrates. Among the eight moss lipoxygenases, only seven were found to be enzymatically active in vitro, two of which selectively used arachidonic acid as the substrate, while the other five preferred alpha-linolenic acid. Based on enzyme assays using a Clark-type oxygen electrode, all of the active lipoxygenases had an optimum pH at 7.0, except for one with highest activity at pH 5.0. HPLC analyses indicated that the two arachidonic acid lipoxygenases form (12S)-hydroperoxy eicosatetraenoic acid as the main product, while the other five lipoxygenases produce mainly (13S)-hydroperoxy octadecatrienoic acid from alpha-linolenic acid. These results suggest that mosses may have both C20 and C18 based oxylipin pathways. Published by Elsevier Ltd.
• Oxidation of oxa and thia fatty acids and related compounds catalysed by 5- and 15-lipoxygenase
  作者：Christopher J. Easton、Thomas A. Robertson、Michael J. Pitt、Deborah A. Rathjen、Antonio Ferrante、Alfred Poulos

  DOI：10.1016/s0968-0896(00)00246-7

  日期：2001.2

  The modified fatty acids, (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid, 3-[(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid, N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine and N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid, all react with soybean 15-lipoxygenase. The products were treated with triphenylphosphine to give alcohols, which were isolated using HPLC. Analysis of the alcohols using negative ion tandem electrospray mass spectrometry, and by comparison with compounds obtained by autoxidation of arachidonic acid, shows that each enzyme catalysed oxidation occurs at the omega -6 position of the substrate. In a similar fashion, it has been found that (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid and N-[(all-Z)-(eicosa-5,8, 11.14-tetraenylthio)]propionic acid each undergoes regioselective oxidation at the carboxyl end of the polyene moiety on treatment with potato 5-lipoxygenase. Neither (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid nor N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid reacts in the presence of this enzyme, while N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine affords the C11' oxidation product. The alcohol derived from (Z,Z,Z)-(octadeca-6,9, 12-trienyloxy)acetic acid using the 15-lipoxygenase reacts at the C6' position with the 5-lipoxygenase. (C) 2001 Elsevier Science Ltd. All rights reserved.
• KUHN, HARTMUT;WIESNER, RAINER, J. CHROMATOGR. , 520,(1990) C. 391-401
  作者：KUHN, HARTMUT、WIESNER, RAINER

  DOI：——

  日期：——