N-油酰基-D-鞘氨醇 | 5966-28-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 中文名称: N-油酰基-D-鞘氨醇
• 英文名称: N-oleoyl-D-sphingosine (erythro form)
• 英文别名: C18:1-ceramide；N-(oleoyl)-ceramide；(Z)-N-[(E,2S,3R)-1,3-dihydroxyoctadec-4-en-2-yl]octadec-9-enamide
• CAS: 5966-28-9
• 化学式: C₃₆H₆₉NO₃
• 分子量: 563.949
• InChiKey: OBFSLMQLPNKVRW-RHPAUOISSA-N

物化性质

• 溶解度：
  氯仿：可溶；二甲基甲酰胺：0.15mg/mL
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  13
• 重原子数：
  40
• 可旋转键数：
  31
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  水 、 N-油酰基-D-鞘氨醇 生成 oleate 、 Sphingosine(1+)
  参考文献：
  名称：

  结核分枝杆菌的重组中性神经酰胺酶的表达，纯化和鉴定。

  摘要：

  神经酰胺酶（CDase）催化神经酰胺（Cer）水解为鞘氨醇（Sph）和脂肪酸。我们已经报道了分枝杆菌CDase（MtCDase）的分子克隆和初步表征（J.Biol.Chem。，274，36616-36622（1999））。为了进一步确定其功能，MtCDase在大肠杆菌中表达并通过Ni-Sepharose和凝胶过滤纯化。纯化的重组酶在SDS-PAGE上显示一条条带，分子量估计为71 kDa。它的最适pH为8.0-9.0，对各种Cers具有相当广泛的特异性。在测试的不同脂肪酸部分的Cer中，由C6-C24脂肪酸组成的Cer被很好地水解，具有单不饱和脂肪酸的Cer的水解程度远高于具有饱和脂肪酸的Cer。使用N-十二烷酰基-7-硝基苯-2-氧杂-1 以3-4-二唑（NBD）-D-赤型鞘氨醇（C12-NBD-Cer）为底物，反应遵循正常的Michaelis-Menten动力学。C12-NBD-Cer的表观Km和Vmax值分别为98

  DOI：

  10.1271/bbb.90645
• 作为产物：
  描述：

  erythro-1-O-benzoylceramide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以92%的产率得到N-油酰基-D-鞘氨醇
  参考文献：
  名称：

  Useful syntheses of erythro- and threo-N-oleoyl-D-sphingosines (ceramides) and galactosylceramides (cerebrosides) from L-serine

  摘要：

  DOI：

  10.1021/jo00335a015

文献信息

• Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases
  作者：AndréR.A. Marques、Mina Mirzaian、Hisako Akiyama、Patrick Wisse、Maria J. Ferraz、Paulo Gaspar、Karen Ghauharali-van der Vlugt、Rianne Meijer、Pilar Giraldo、Pilar Alfonso、Pilar Irún、Maria Dahl、Stefan Karlsson、Elena V. Pavlova、Timothy M. Cox、Saskia Scheij、Marri Verhoek、Roelof Ottenhoff、CindyP.A.A. van Roomen、Navraj S. Pannu、Marco van Eijk、Nick Dekker、Rolf G. Boot、Herman S. Overkleeft、Edward Blommaart、Yoshio Hirabayashi、Johannes M. Aerts

  DOI：10.1194/jlr.m064923

  日期：2016.3

  GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C disease, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation

  膜脂葡萄糖神经酰胺（GlcCer）不断形成和降解。细胞表达两种降解 GlcCer 的 β-葡萄糖苷酶，葡萄糖脑苷脂酶 (GBA) 和 GBA2，分别位于溶酶体内部和外部。在这里，我们证明通过转葡萄糖基化，GBA 和 GBA2 都能够在体外催化葡萄糖基部分从 GlcCer 转移到胆固醇，反之亦然。此外，使用 LC-MS/MS 和 (13)C6 标记的​​ GlcChol 作为内标，证明了小鼠组织和人血浆中 1-O-胆固醇-β-D-吡喃葡萄糖苷 (GlcChol) 的自然存在。在细胞中，抑制 GBA 会增加 GlcChol，而抑制 GBA2 会减少葡糖基化甾醇。同样，在 GBA2 缺陷小鼠中，GlcChol 减少。通过抑制 GlcCer 合酶消耗 GlcCer 会降低细胞中的 GlcChol，同样在抑制剂治疗的戈谢病患者的血浆中也是如此。在患有 Niemann-Pick C 型疾病（一种以胆固
• The Synthesis and Biological Characterization of a Ceramide Library
  作者：Young-Tae Chang、Jaehwa Choi、Sheng Ding、Eva E. Prieschl、Thomas Baumruker、Jae-Mok Lee、Sung-Kee Chung、Peter G. Schultz

  DOI：10.1021/ja017576o

  日期：2002.3.1

  A facile synthesis of a combinatorial ceramide library and their activities in the NF-kappaB pathway and in apoptosis induction/prevention were demonstrated. A novel NF-kappaB activating molecule was discovered among ceramide containing beta-galactose, and the structural requirements of ceramides for apoptosis induction was elucidated.
• Cholesterol glucosylation is catalyzed by transglucosylation reaction of β-glucosidase 1
  作者：Hisako Akiyama、Susumu Kobayashi、Yoshio Hirabayashi、Kimiko Murakami-Murofushi

  DOI：10.1016/j.bbrc.2013.10.145

  日期：2013.11

  Cholesteryl glucoside (beta-ChIGIc), a monoglucosylated derivative of cholesterol, is involved in the regulation of heat shock responses. beta-ChIGIc, which is rapidly induced in response to heat shock, activates heat shock transcription factor 1 (HSF1) leading to the expression of heat shock protein 70 (HSP70) in human fibroblasts. Identification and biochemical characterization of the enzyme responsible for beta-ChIGIc formation is important for a complete understanding of the molecular mechanisms leading to HSP70-induction following heat shock. Recently, we demonstrated that beta-ChIGIc synthesis is not dependent on UDP-Glucose but glucosylceramide (GlcCer) in animal tissue and human fibroblasts. In this study, we examined the possibility of glucocerebrosidase, a GIcCer-degrading glycosidase, acting as beta-ChIGIc-synthesizing enzyme. Overexpression of beta-glucosidase (GBA1, lysosomal acid beta-glucocerebrosidase) led to an increase in cholesterol glucosylation activity in human fibroblasts. Using a cell line generated from type 2 Gaucher disease patients with severe defects in GBA1 activity, we found that cholesterol glucosylation activity was very low in the cells and the overexpression of GBA1 rescued the activity. In addition, purified recombinant GBA1 exhibits conduritol B-epoxide-sensitive cholesterol glucosylation activity. The optimum pH and temperature for cholesterol glucosylation by GBA1 were at about 5.3 and 43 C, respectively. Short chain C8:0-GIcCer was the most effective donor for cholesterol glucosylation activity among GIcCer containing saturated fatty acid (C8:0 to C18:0) tested. GlcCer containing mono-unsaturated fatty acid was more preferred substrate for cholesterol glucosylation when compared with GIcCer containing same chain length of saturated fatty acid. These results demonstrate, for the first time, a novel function of GBA1 as a beta-ChIGIc-synthesizing enzyme. Therefore, our results also reveal a new pathway for glycolipid metabolism in mammals. (C) 2013 Elsevier Inc. All rights reserved.
• Substrate Specificity, Membrane Topology, and Activity Regulation of Human Alkaline Ceramidase 2 (ACER2)
  作者：Wei Sun、Junfei Jin、Ruijuan Xu、Wei Hu、Zdzislaw M. Szulc、Jacek Bielawski、Lina M. Obeid、Cungui Mao

  DOI：10.1074/jbc.m109.069203

  日期：2010.3

  Human alkaline ceramidase 2 (ACER2) plays an important role in cellular responses by regulating the hydrolysis of ceramides in cells. Here we report its biochemical characterization, membrane topology, and activity regulation. Recombinant ACER2 was expressed in yeast mutant cells (Delta ypc1 Delta ydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressiong yeast cells were used to biochemically characterize ACER2. ACER2 catalyzed the hydrolysis of various ceramides and followed Michaelis-Menten kinetics. ACER2 required Ca2+ for both its in vitro and cellular activities. ACER2 has 7 putative transmembrane domains, and its amino (N) and carboxyl (C) termini were found to be oriented in the lumen of the Golgi complex and cytosol, respectively. ACER2 mutant (ACER2 Delta N36) lacking the N-terminal tail (the first 36 amino acid residues) exhibited undetectable activity and was mislocalized to the endoplasmic reticulum, suggesting that the N-terminal tail is necessary for both ACER2 activity and Golgi localization. ACER2 mutant (ACER2 Delta N13) lacking the first 13 residues was also mislocalized to the endoplasmic reticulum although it retained ceramidase activity. Overexpression of ACER2, ACER2 Delta N13, but not ACER2 Delta N36 increased the release of sphingosine 1-phosphate from cells, suggesting that its mislocalization does not affect the ability of ACER2 to regulate sphingosine 1-phosphate secretion. However, overexpression of ACER2 but not ACER2 Delta N13 or ACER2 Delta N36 inhibited the glycosylation of integrin beta 1 subunit and Lamp1, suggesting that its mistargeting abolishes the ability of ACER2 to regulation protein glycosylation. These data suggest that ACER2 has broad substrate specificity and requires Ca2+ for its activity and that ACER2 has the cytosolic C terminus and luminal N terminus, which are essential for its activity, correct cellular localization, and regulation for protein glycosylation.
• Biochemical Characterization of the Reverse Activity of Rat Brain Ceramidase
  作者：Samer El Bawab、Helene Birbes、Patrick Roddy、Zdzislaw M. Szulc、Alicja Bielawska、Yusuf A. Hannun

  DOI：10.1074/jbc.m009331200

  日期：2001.5

  We have previously purified a membrane-bound ceramidase from rat brain and recently cloned the human homologue, We also observed that the same enzyme is able to catalyze the reverse reaction of ceramide synthesis. To obtain insight into the biochemistry of this enzyme, we characterized in this study this reverse activity. Using sphingosine and palmitic acid as substrates, the enzyme exhibited Michaelis-Menten kinetics; however, the enzyme did not utilize palmitoyl-CoA as substrate. Also, the activity was not inhibited in vitro and in cells by fumonisin B-1, an inhibitor of the CoA-dependent ceramide synthase, The enzyme showed a narrow pH optimum in the neutral range, and there was very low activity in the alkaline range. Substrate specificity studies were performed, and the enzyme showed the highest activity with D-erythro-sphingosine (K-m of 0.16 mol %, and V-max of 0.3 mu mol/min/mg), but D-erythro-dihydrosphingosine and the three unnatural stereoisomers of sphingosine were poor substrates. The specificity for the fatty acid was also studied, and the highest activity was observed for myristic acid with a K-m of 1.7 mol % and a V-max of 0.63 mu mol/min/mg, Kinetic studies were performed to investigate the mechanism of the reaction, and Lineweaver-Burk plots indicated a sequential mechanism. Two competitive inhibitors of the two substrates were identified, L-erythro-sphingosine and myristaldehyde, and inhibition studies indicated that the reaction followed a random sequential mechanism. The effect of lipids were also tested. Most of these lipids showed moderate inhibition, whereas the effects of phosphatidic acid and cardiolipin were more potent with total inhibition at around 2.5-5 mol %, Paradoxically, cardiolipin stimulated ceramidase activity. These results define the biochemical characteristics of this reverse activity. The results are discussed in view of a possible regulation of this enzyme by the intracellular pH or by an interaction with cardiolipin and/or phosphatidic acid.