[1-14C]-花生四烯酸 | 3435-81-2

• 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: [1-14C]-花生四烯酸
• 英文名称: [1-14C]-arachidonic acid
• 英文别名: Arachidonic acid-carboxy-14C；(5Z,8Z,11Z,14Z)-(114C)icosa-5,8,11,14-tetraenoic acid
• CAS: 3435-81-2
• 化学式: C₂₀H₃₂O₂
• 分子量: 306.462
• InChiKey: YZXBAPSDXZZRGB-XJAQZXCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  22
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi,F,R
• 安全说明：
  S16,S26,S36,S7
• 危险类别码：
  R11,R36/37/38

反应信息

• 作为反应物：
  描述：

  [1-14C]-花生四烯酸 在 hematin 、 hexahistidine-tagged human prostaglandin endoperoxide H synthase-2 apo-form 、 氧气 、 三羟甲基氨基甲烷盐酸盐 、 苯酚 作用下， 以 水 为溶剂， 生成 [1-14C]prostaglandin H2
  参考文献：
  名称：

  Human Cyclooxygenase-2 Is a Sequence Homodimer That Functions as a Conformational Heterodimer

  摘要：

  Prostaglandin endoperoxide H synthases 1 and 2, also known as cyclooxygenases (COXs) 1 and 2, convert arachidonic acid (AA) to prostaglandin endoperoxide H-2. Prostaglandin endoperoxide H synthases are targets of nonspecific nonsteroidal anti-inflammatory drugs and COX-2-specific inhibitors called coxibs. PGHS-2 is a sequence homodimer. Each monomer has a peroxidase and a COX active site. We find that human PGHS-2 functions as a conformational heterodimer having a catalytic monomer (E-cat) and an allosteric monomer (E-allo). Heme binds tightly only to the peroxidase site of E-cat, whereas substrates, as well as certain inhibitors (e.g. celecoxib), bind the COX site of E-cat. E-cat is regulated by E-allo in a manner dependent on what ligand is bound to E-allo. Substrate and nonsubstrate fatty acids (FAs) and some COX inhibitors (e. g. naproxen) preferentially bind to the COX site of E-allo. AA can bind to E-cat and E-allo, but the affinity of AA for E-allo is 25 times that for E-cat. Palmitic acid, an efficacious stimulator of human PGHS-2, binds only E-allo in palmitic acid/murine PGHS-2 co-crystals. Nonsubstrate FAs can potentiate or attenuate actions of COX inhibitors depending on the FA and whether the inhibitor binds E-cat or E-allo. Our studies suggest that the concentration and composition of the free FA pool in the environment in which PGHS-2 functions in cells, the FA tone, is a key factor regulating PGHS-2 activity and its responses to COX inhibitors. We suggest that differences in FA tone occurring with different diets will likely affect both baseline prostanoid synthesis and responses to COX inhibitors.

  DOI：

  10.1074/jbc.m111.231969
• 作为产物：
  描述：

  [(14)C]1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine 在 乙二醇双(2-氨基乙基醚)四乙酸 、 human C-terminal His6-tagged cytosolic phospholipase A2-α (group IVA) 、 potassium chloride 、 calcium chloride 作用下， 反应 0.17h， 生成 [1-14C]-花生四烯酸
  参考文献：
  名称：

  Interfacial Kinetic and Binding Properties of Mammalian Group IVB Phospholipase A2 (cPLA2β) and Comparison with the Other cPLA2 Isoforms

  摘要：

  The cytosolic (group IV) phospholipase A(2) (cPLA(2)s) family contains six members. We have prepared recombinant proteins for human alpha, mouse beta, human gamma, human delta, human epsilon, and mouse zeta cPLA(2)s and have studied their interfacial kinetic and binding properties in vitro. Mouse cPLA(2)beta action on phosphatidylcholine vesicles is activated by anionic phosphoinositides and cardiolipin but displays a requirement for Ca2+ only in the presence of cardiolipin. This activation pattern is explained by the effects of anionic phospholipids and Ca2+ on the interfacial binding of mouse cPLA(2)beta and its C2 domain to vesicles. Ca2+ dependent binding of mouse cPLA(2)beta to cardiolipin-containing vesicles requires a patch of basic residues near the Ca2+-binding surface loops of the C2 domain, but binding to phosphoinositide-containing vesicles does not depend on any specific cluster of basic residues. Human cPLA(2)delta also displays Ca2+- and cardiolipin-enhanced interfacial binding and activity. The lysophospholipase, phospholipase A(1), and phospholipase A(2) activities of the full set of mammalian cPLA(2)s were quantified. The relative level of these activities is very different among the isoforms, and human cPLA(2)delta stands out as having relatively high phospholipase A(1) activity. We also tested the susceptibility of all cPLA(2) family members to a panel of previously reported inhibitors of human cPLA(2)alpha and analogs of these compounds. This led to the discovery of a potent and selective inhibitor of mouse cPLA(2)beta. These in vitro studies help determine the regulation and function of the cPLA(2) family members.

  DOI：

  10.1074/jbc.m110.165647

文献信息

• 8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases
  作者：Jing Jin、William E. Boeglin、Jin K. Cha、Alan R. Brash

  DOI：10.1194/jlr.m022863

  日期：2012.2

  of fatty acid hydroperoxides to epoxyalcohols is a well known secondary reaction of lipoxygenases, described for S-specific lipoxygenases forming epoxyalcohols with a trans-epoxide configuration. Here we report on R-specific lipoxygenase synthesis of a cis-epoxyalcohol. Although arachidonic and dihomo-γ-linolenic acids are metabolized by extracts of the Caribbean coral Plexaura homomalla via 8R-lipoxygenase

  脂肪酸氢过氧化物转化为环氧醇是众所周知的脂氧合酶次级反应，描述了 S 特异性脂氧合酶形成具有反式环氧化物构型的环氧醇。在这里，我们报告了顺式环氧醇的 R 特异性脂氧合酶合成。尽管花生四烯酸和二高-γ-亚麻酸由加勒比珊瑚 Plexaura homomalla 的提取物通过 8R-脂氧合酶和丙二烯氧化合酶活性代谢，但 20:3ω6 形成了另外一个突出的产物，通过比较使用 UV、GC-MS 和 NMR 进行鉴定合成标准为 8R,9S-cis-epoxy-10S-erythro-hydroxy-eicosa-11Z,14Z-dienoic acid。(18)O 标记的 8R-氢过氧化物的两个氧都保留在产物中，表明具有氢过氧化物异构酶活性。重组丙二烯氧化合酶仅从 8R-氢过氧-20:3ω6 形成丙二烯环氧化物，而两种不同的 8R-脂肪氧化酶选择性地产生环氧醇。提出了一种生物合成方案，其中需要部分旋转
• Evidence for conversion of arachidonic acid to hydroxyicosatetraenoic acids by a cell-free homogenate from maize seedlings
  作者：Boris Janistyn

  DOI：10.1016/0031-9422(90)85165-c

  日期：1990.1
• Human Cyclooxygenase-2 Is a Sequence Homodimer That Functions as a Conformational Heterodimer
  作者：Liang Dong、Alex J. Vecchio、Narayan P. Sharma、Brice J. Jurban、Michael G. Malkowski、William L. Smith

  DOI：10.1074/jbc.m111.231969

  日期：2011.5

  Prostaglandin endoperoxide H synthases 1 and 2, also known as cyclooxygenases (COXs) 1 and 2, convert arachidonic acid (AA) to prostaglandin endoperoxide H-2. Prostaglandin endoperoxide H synthases are targets of nonspecific nonsteroidal anti-inflammatory drugs and COX-2-specific inhibitors called coxibs. PGHS-2 is a sequence homodimer. Each monomer has a peroxidase and a COX active site. We find that human PGHS-2 functions as a conformational heterodimer having a catalytic monomer (E-cat) and an allosteric monomer (E-allo). Heme binds tightly only to the peroxidase site of E-cat, whereas substrates, as well as certain inhibitors (e.g. celecoxib), bind the COX site of E-cat. E-cat is regulated by E-allo in a manner dependent on what ligand is bound to E-allo. Substrate and nonsubstrate fatty acids (FAs) and some COX inhibitors (e. g. naproxen) preferentially bind to the COX site of E-allo. AA can bind to E-cat and E-allo, but the affinity of AA for E-allo is 25 times that for E-cat. Palmitic acid, an efficacious stimulator of human PGHS-2, binds only E-allo in palmitic acid/murine PGHS-2 co-crystals. Nonsubstrate FAs can potentiate or attenuate actions of COX inhibitors depending on the FA and whether the inhibitor binds E-cat or E-allo. Our studies suggest that the concentration and composition of the free FA pool in the environment in which PGHS-2 functions in cells, the FA tone, is a key factor regulating PGHS-2 activity and its responses to COX inhibitors. We suggest that differences in FA tone occurring with different diets will likely affect both baseline prostanoid synthesis and responses to COX inhibitors.
• Interfacial Kinetic and Binding Properties of Mammalian Group IVB Phospholipase A2 (cPLA2β) and Comparison with the Other cPLA2 Isoforms
  作者：Farideh Ghomashchi、Gajendra S. Naika、James G. Bollinger、Ahmed Aloulou、Matthias Lehr、Christina C. Leslie、Michael H. Gelb

  DOI：10.1074/jbc.m110.165647

  日期：2010.11

  The cytosolic (group IV) phospholipase A(2) (cPLA(2)s) family contains six members. We have prepared recombinant proteins for human alpha, mouse beta, human gamma, human delta, human epsilon, and mouse zeta cPLA(2)s and have studied their interfacial kinetic and binding properties in vitro. Mouse cPLA(2)beta action on phosphatidylcholine vesicles is activated by anionic phosphoinositides and cardiolipin but displays a requirement for Ca2+ only in the presence of cardiolipin. This activation pattern is explained by the effects of anionic phospholipids and Ca2+ on the interfacial binding of mouse cPLA(2)beta and its C2 domain to vesicles. Ca2+ dependent binding of mouse cPLA(2)beta to cardiolipin-containing vesicles requires a patch of basic residues near the Ca2+-binding surface loops of the C2 domain, but binding to phosphoinositide-containing vesicles does not depend on any specific cluster of basic residues. Human cPLA(2)delta also displays Ca2+- and cardiolipin-enhanced interfacial binding and activity. The lysophospholipase, phospholipase A(1), and phospholipase A(2) activities of the full set of mammalian cPLA(2)s were quantified. The relative level of these activities is very different among the isoforms, and human cPLA(2)delta stands out as having relatively high phospholipase A(1) activity. We also tested the susceptibility of all cPLA(2) family members to a panel of previously reported inhibitors of human cPLA(2)alpha and analogs of these compounds. This led to the discovery of a potent and selective inhibitor of mouse cPLA(2)beta. These in vitro studies help determine the regulation and function of the cPLA(2) family members.