神经酸酰胺 | 54164-50-0

• 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: 神经酸酰胺
• 英文名称: C24:1-ceramide
• 英文别名: Cer(d18:1/24:1(15Z))；(Z)-N-[(E,2S,3R)-1,3-dihydroxyoctadec-4-en-2-yl]tetracos-15-enamide
• CAS: 54164-50-0
• 化学式: C₄₂H₈₁NO₃
• 分子量: 648.11
• InChiKey: VJSBNBBOSZJDKB-KPEYJIHVSA-N

物化性质

• 熔点：
  80-82°C
• 溶解度：
  氯仿（微溶）、甲醇（微溶、加热）
• 物理描述：
  Solid
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  16.3
• 重原子数：
  46
• 可旋转键数：
  37
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2922199090
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  神经酸酰胺 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 以33%的产率得到N-tetracos-15(Z)-enyl-sphingosine
  参考文献：
  名称：

  Formation of high-axial-ratio-microstructures from natural and synthetic sphingolipids

  摘要：

  Amphiphiles that form high-axial-ratio-microstructures (HARMs) are being considered as novel materials for controlled release of drugs and other biologically functional molecules. HARMs consisting of tubules, ribbons, solid rods and helices are formed from sphingolipids by addition of water to a solution of amphiphile in DMF. Single molecular species of galactocerebroside (GalCer) containing long unsaturated fatty acid chains or natural GalCer containing mixed-length, non-hydroxy fatty acids (NFA-GalCer) or alpha-hydroxy fatty acids (HFA-GalCer) form cylindrical structures. In contrast, single molecular species of GalCer containing long saturated fatty acids form ribbons and helices. GalCer HARMs are typically under 100 nm in diameter and have lengths of several microns. The importance of the amide of GalCer for HARM formation was evaluated using psychosine, which forms solid fibers, whereas sphingosine and an analog of GalCer in which the amide is reduced to a secondary amine form amorphous aggregates. Single molecular species of ceramide containing long unsaturated fatty acid chains form cylindrical structures, whereas those with long saturated fatty acids form ribbons and helices. Short chain saturated ceramide also forms cylindrical structures. GalCer analogs with N-acetyl-glycine in place of the galactose form fibers whereas those with N-acetyl-proline yield amorphous material. The N-acetyl-proline-containing amphiphile can de doped into pure GalCer or NFA-GalCer without perturbing tubule formation. (C) 1997 Elsevier Science Ireland Ltd.

  DOI：

  10.1016/s0009-3084(97)00042-x
• 作为产物：
  描述：

  神经酸 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 神经酸酰胺
  参考文献：
  名称：

  Formation of high-axial-ratio-microstructures from natural and synthetic sphingolipids

  摘要：

  Amphiphiles that form high-axial-ratio-microstructures (HARMs) are being considered as novel materials for controlled release of drugs and other biologically functional molecules. HARMs consisting of tubules, ribbons, solid rods and helices are formed from sphingolipids by addition of water to a solution of amphiphile in DMF. Single molecular species of galactocerebroside (GalCer) containing long unsaturated fatty acid chains or natural GalCer containing mixed-length, non-hydroxy fatty acids (NFA-GalCer) or alpha-hydroxy fatty acids (HFA-GalCer) form cylindrical structures. In contrast, single molecular species of GalCer containing long saturated fatty acids form ribbons and helices. GalCer HARMs are typically under 100 nm in diameter and have lengths of several microns. The importance of the amide of GalCer for HARM formation was evaluated using psychosine, which forms solid fibers, whereas sphingosine and an analog of GalCer in which the amide is reduced to a secondary amine form amorphous aggregates. Single molecular species of ceramide containing long unsaturated fatty acid chains form cylindrical structures, whereas those with long saturated fatty acids form ribbons and helices. Short chain saturated ceramide also forms cylindrical structures. GalCer analogs with N-acetyl-glycine in place of the galactose form fibers whereas those with N-acetyl-proline yield amorphous material. The N-acetyl-proline-containing amphiphile can de doped into pure GalCer or NFA-GalCer without perturbing tubule formation. (C) 1997 Elsevier Science Ireland Ltd.

  DOI：

  10.1016/s0009-3084(97)00042-x

文献信息

• The relationship between the structure of the headgroup of sphingolipids and their ability to form complex high axial ratio microstructures
  作者：Alex S Goldstein、Michael H Gelb、Paul Yager

  DOI：10.1016/s0009-3084(00)00204-8

  日期：2001.1

  examined for their ability to form complex high axial ratio microstructures (CHARMS), potential drug delivery vehicles. In general, if the modified ceramide had either a hydrogen bond donor or acceptor at C-1 and C-3, including hydrophobic or hydrophilic groups attached to C-1 microstructures formed. Tolerated groups include amides, esters, sulfonates, and ethers. If modification at C-3 added significant

  制备了具有化学修饰的极性头基的神经酰胺，并检查了其形成复杂的高轴向比微结构（CHARMS）（潜在的药物递送载体）的能力。通常，如果改性的神经酰胺在C-1和C-3处具有氢键供体或受体，包括与形成的C-1微结构相连的疏水或亲水基团。容许的基团包括酰胺，酯，磺酸盐和醚。如果C-3处的修饰增加了大量的体积（大于4个碳原子，而与亲水性无关），则会形成无定形聚集体。具有通过循环结构桥接的C-1和C-3的神经酰胺也可形成微结构。通过使用具有胺头基的鞘脂，可以在形成后共价修饰CHARM。
• Expression, Purification, and Characterization of a Recombinant Neutral Ceramidase from<i>Mycobacterium tuberculosis</i>
  作者：Nozomu OKINO、Rie IKEDA、Makoto ITO

  DOI：10.1271/bbb.90645

  日期：2010.2.23

  It had a pH optimum at 8.0-9.0 and quite broad specificity for various Cers. Of the Cers of different fatty acid moieties tested, those composed of C6-C24 fatty acids were well hydrolyzed, and Cers with mono unsaturated fatty acids were much more hydrolyzed than those with saturated fatty acids. Using N-dodecanoyl-7-nitrobenz-2-oxa-1,3-4-diazole (NBD)-D-erythro-sphingosine (C12-NBD-Cer) as substrates

  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
• ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis
  作者：Yusuke Ohno、Shota Suto、Masao Yamanaka、Yukiko Mizutani、Susumu Mitsutake、Yasuyuki Igarashi、Takayuki Sassa、Akio Kihara

  DOI：10.1073/pnas.1005572107

  日期：2010.10.26

  Very long-chain fatty acids (VLCFAs) exert a variety of cellular functions and are associated with numerous diseases. However, the precise pathway behind their elongation has remained elusive. Moreover, few regulatory mechanisms for VLCFAs synthesis have been identified. Elongases catalyze the first of four steps in the VLCFA elongation cycle; mammals have seven elongases (ELOVL1–7). In the present study, we determined the precise substrate specificities of all the ELOVLs by in vitro analyses. Particularly notable was the high activity exhibited by ELOVL1 toward saturated and monounsaturated C20- and C22-CoAs, and that it was essential for the production of C24 sphingolipids, which are unique in their capacity to interdigitate within the membrane as a result of their long chain length. We further established that ELOVL1 activity is regulated with the ceramide synthase CERS2, an enzyme essential for C24 sphingolipid synthesis. This regulation may ensure that the production of C24-CoA by elongation is coordinated with its utilization. Finally, knockdown of ELOVL1 caused a reduction in the activity of the Src kinase LYN, confirming that C24-sphingolipids are particularly important in membrane microdomain function.

  非常长的链脂肪酸(VLCFAs)具有多种细胞功能并与许多疾病相关。然而，它们的延长路径仍然不清楚。此外，VLCFAs合成的少数调节机制已被确定。Elongases在VLCFA延长循环的四个步骤中催化第一个步骤；哺乳动物有七个elongases(ELOVL1-7)。在本研究中，我们通过体外分析确定了所有ELOVLs的精确底物特异性。特别值得注意的是，ELOVL1对饱和和单不饱和C20和C22-CoAs表现出的高活性，而且对于C24鞘脂的产生是必不可少的，这些鞘脂由于其长链长度而具有在膜内交错的能力是独特的。我们进一步确定ELOVL1活性由鞘脂合酶CERS2调节，这是C24鞘脂合成所必需的酶。这种调节可能确保通过延长产生的C24-CoA与其利用协调。最后，ELOVL1的沉默导致Src激酶LYN的活性降低，证实C24鞘脂在膜微区功能中特别重要。
• 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.
• Role for Mammalian Neutral Sphingomyelinase 2 in Confluence-induced Growth Arrest of MCF7 Cells
  作者：Norma Marchesini、Walid Osta、Jacek Bielawski、Chiara Luberto、Lina M. Obeid、Yusuf A. Hannun

  DOI：10.1074/jbc.m313662200

  日期：2004.6

  Recently, we reported that neutral sphingomyelinase 2 (nSMase2) functions as a bona fide neutral sphingomyelinase and that overexpression of nSMase2 in MCF7 breast cancer cells caused a decrease in cell growth (Marchesini, N., Luberto, C., and Hannun, Y. A. (2003) J. Biol. Chem. 278, 13775-13783). In this study, the role of endogenous nSMase2 in regulating growth arrest was investigated. The results show that endogenous nSMase2 mRNA was up-regulated similar to5-fold when MCF7 cells became growth-arrested at confluence, and total neutral SMase activity was increased by 119 +/- 41% with respect to control. Cell cycle analysis showed that up-regulation of endogenous nSMase2 correlated with G(0)/G(1) cell cycle arrest and an increase in total ceramide levels (2.4-fold). Analysis of ceramide species showed that confluence caused selective increases in very long chain ceramide C-24:1 (370 +/- 54%) and C-24:0 (266 +/- 81%) during arrest. The role of endogenous nSMase2 in growth regulation and ceramide metabolism was investigated using short interfering RNA (siRNA)-mediated loss-of-function analysis. Down-regulation of nSMase2 with specific siRNA increased the cell population of cells in S phase of the cell cycle by 59 +/- 14% and selectively reverted the effects of growth arrest on the increase in levels of very long chain ceramides. Mechanistically, confluence arrest also induced hypophosphorylation of the retinoblastoma protein (6-fold) and induction of p21(WAF1) (3-fold). Downregulation of nSMase2 with siRNA largely prevented the dephosphorylation of the retinoblastoma protein and the induction of p21(WAF1), providing a link between the action of nSMase2 and key regulators of cell cycle progression. Moreover, studies on nSMase2 localization in MCF7 cells showed that nSMase2 distributed throughout the cells in subconfluent, proliferating cultures. In contrast, nSMase2 became nearly exclusively located at the plasma membrane in confluent, contact-inhibited cells. Hence, we demonstrate for the first time that nSMase2 functions as a growth suppressor in MCF7 cells, linking confluence to the G(0)/G(1) cell cycle check point.