(5Z,8Z,11R,12E,14Z)-11-羟基二十碳-5,8,12,14-四烯酸 | 73347-43-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (5Z,8Z,11R,12E,14Z)-11-羟基二十碳-5,8,12,14-四烯酸
• 英文名称: (11R)-hydroxyeicosatetraenoic acid
• 英文别名: 11(R)-Hete；(5Z,8Z,11R,12E,14Z)-11-hydroxyicosa-5,8,12,14-tetraenoic acid
• CAS: 73347-43-0
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: GCZRCCHPLVMMJE-WXMXURGXSA-N

物化性质

• 闪点：
  14 °C
• 溶解度：
  0.1 M Na2CO3：2 mg/mL； DMF：可混溶； DMSO：可混溶；乙醇：可混溶； PBS pH 7.2：0.8 mg/mL

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

制备方法与用途

(R)-HETE是一种由花生四烯酸衍生而来的化合物。

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (5Z,8Z,11R,12E,14Z)-11-羟基二十碳-5,8,12,14-四烯酸 以 乙醚 为溶剂， 反应 0.01h， 生成 (5Z,8Z,12E,14Z)-(R)-11-Hydroxy-icosa-5,8,12,14-tetraenoic acid methyl ester
  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：

  花生四烯酸 在 L-半胱氨酸 、 Escherichia coli cells expressing arachidonate 11R-lipoxygenase from Nostoc sp. 作用下， 以 乙醇 为溶剂， 生成 (5Z,8Z,11R,12E,14Z)-11-羟基二十碳-5,8,12,14-四烯酸
  参考文献：
  名称：

  Production of11R‐hydroxyeicosatetraenoicacid from arachidonic acid byEscherichia colicells expressing arachidonate11R‐lipoxygenasefromNostocsp.

  摘要：

  AbstractLinoleate 9R‐lipoxygenase (9R‐LOX) from Nostoc sp. SAG 25.82 was identified as arachidonate (ARA) 11R‐LOX by the determination of the product obtained from the conversion of ARA. The specific activity and catalytic efficiency (kcat/Km) of the enzyme for C20 and C22 polyunsaturated fatty acids followed the order ARA > eicosapentaenoic acid > docosahexaenoic acid. The production of the lipid mediator 11R‐hydroxyeicosatetraenoic acid (11R‐HETE) was performed using Escherichia coli cells expressing ARA 11R‐LOX from Nostoc sp. The reaction conditions, such as pH, temperature, solvent and its concentration, and substrate and cell concentrations, were optimized using the recombinant cells, and the optimal conditions for the production of 11R‐HETE from ARA were pH 7.0, 25°C, 10 g L−1 cells, 5.0 mM ARA, 4% (v/v) ethanol, and 10 mM cysteine as a reducing agent. Under these optimized conditions, E. coli cells expressing 11R‐LOX converted 5.0 mM ARA into 4.74 mM 11R‐HETE in 60 min, with a molar conversion yield of 95% a volumetric productivity of 79 μM min−1 and a specific productivity of 7.9 μM min−1 g−1. To the best of our knowledge, this is the first report on the quantitative biotechnological production of 11R‐HETE.

  DOI：

  10.1002/aocs.12572

文献信息

• 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.
• Crystal Structure of a Lipoxygenase in Complex with Substrate
  作者：David B. Neau、Gunes Bender、William E. Boeglin、Sue G. Bartlett、Alan R. Brash、Marcia E. Newcomer

  DOI：10.1074/jbc.m114.599662

  日期：2014.11

  Background: Lipoxygenases (LOX) catalyze the oxygenation of polyunsaturated fatty acids but generate distinct products from a common substrate. Results: We report the first structure of a LOX-substrate complex. Conclusion: The structure provides a context for understanding product specificity in enzymes that metabolize arachidonic acid. Significance: With roles in the production of potent lipid mediators, LOX are targets for drug design.Lipoxygenases (LOX) play critical roles in mammalian biology in the generation of potent lipid mediators of the inflammatory response; consequently, they are targets for the development of isoform-specific inhibitors. The regio- and stereo-specificity of the oxygenation of polyunsaturated fatty acids by the enzymes is understood in terms of the chemistry, but structural observation of the enzyme-substrate interactions is lacking. Although several LOX crystal structures are available, heretofore the rapid oxygenation of bound substrate has precluded capture of the enzyme-substrate complex, leaving a gap between chemical and structural insights. In this report, we describe the 2.0 angstrom resolution structure of 8R-LOX in complex with arachidonic acid obtained under anaerobic conditions. Subtle rearrangements, primarily in the side chains of three amino acids, allow binding of arachidonic acid in a catalytically competent conformation. Accompanying experimental work supports a model in which both substrate tethering and cavity depth contribute to positioning the appropriate carbon at the catalytic machinery.
• 2,4-Decadienals are produced via (R)-11-HPITE from arachidonic acid in marine green alga Ulva conglobata
  作者：Yoshihiko Akakabe、Kenji Matsui、Tadahiko Kajiwara

  DOI：10.1016/s0968-0896(03)00364-x

  日期：2003.8

  Marine green alga Ulva conglobata was investigated for the biogeneration of oxygenated products from exogenously added arachidonic acid (ARA). A crude enzyme from the alga afforded the detectable amount of a hydroperoxyicosatetraenoic acid (HPITE), which was identified as (R)-11-HPITE by HPLC and GC-MS. Headspace-SPME method indicated that ARA was selectively used to form 2,4-decadienals. These results showed that 2,4-decadienals are produced via (R)-11-HPITE from ARA exclusively. (C) 2003 Elsevier Ltd. All rights reserved.
• Stereospecific total synthesis of 11(R)-HETE (2), lipoxygenation product of arachidonic acid via the prostaglandin pathway
  作者：E. J. Corey、Jahyo Kang

  DOI：10.1021/ja00405a071

  日期：1981.7
• Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2
  作者：Surafel Mulugeta、Takashi Suzuki、Noemi Tejera Hernandez、Markus Griesser、William E. Boeglin、Claus Schneider

  DOI：10.1194/jlr.m001719

  日期：2010.3

  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.