C26-二氢神经酰胺 | 182362-38-5

• 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: C26-二氢神经酰胺
• 中文别名: N-[(2S,3R)-1,3-二羟基十八烷-2-基]二十六烷酰胺；2,2,2',2'-四甲基-2H,2'H-5,5'-联苯并[h]色烯-6,6'-二醇
• 英文名称: N-(hexacosanoyl)-sphinganine
• 英文别名: N-[(2S,3R)-1,3-dihydroxyoctadecan-2-yl]hexacosanamide
• CAS: 182362-38-5
• 化学式: C₄₄H₈₉NO₃
• 分子量: 680.2
• InChiKey: NWERZHCPHDHUMO-WZYYJWNZSA-N

物化性质

• 熔点：
  100 - 102°C
• 沸点：
  768.2±50.0 °C(Predicted)
• 密度：
  0.899±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  18.8
• 重原子数：
  48
• 可旋转键数：
  41
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.98
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) 、 C26-二氢神经酰胺 生成 a 1,2-diacyl-sn-glycerol 、 N-(hexacosanoyl)-sphinganine-1-(1D-myo-inositol)
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  hexacosanoyl-CoA(4-) 、 Sphinganine(1+) 生成 coenzyme A 、 氢(+1)阳离子 、 C26-二氢神经酰胺
  参考文献：
  名称：

  Mammalian Lass6 and its related family members regulate synthesis of specific ceramides

  摘要：

  Lass（长寿保证同源物）家族成员在真核生物中高度保守，在神经酰胺合成中发挥作用。在小鼠体内，至少有五个 Lass 家族成员，即 Lass1、Lass2、Lass4、Lass5 和迄今尚未定性的 Lass6。为了研究每个 Lass 成员在神经酰胺合成中的特定作用，我们克隆了这五种小鼠蛋白。在培养细胞中过度生产任何一种 Lass 蛋白都会导致细胞神经酰胺的增加，但产生的神经酰胺种类各不相同。过量生产 Lass1 会优先增加 C18:0 神经酰胺的含量，而过量生产 Lass2 和 Lass4 则会增加较长神经酰胺的含量，如 C22:0 和 C24:0 神经酰胺。Lass5 和 Lass6 产生较短的神经酰胺种类（C14:0- 和 C16:0-神经酰胺）；但是，它们对饱和/不饱和脂肪酰基-CoA 的底物偏好不同。除了底物偏好的差异，我们还通过 Northern 印迹技术证明了 Lass 家族成员在不同组织中的表达差异。此外，我们还发现 Lass 蛋白在糖基化方面存在差异。在五个成员中，只有 Lass2、Lass5 和 Lass6 在其 N 端 Asn 残基上进行了 N-糖基化。一些 Lass 蛋白发生 N-糖基化提供了拓扑学上的启示，表明 Lass 家族成员的 N 端可能面向内质网膜的腔侧。此外，基于蛋白酶 K 消化试验，我们证明 Lass6 的 C 端面向膜的细胞质一侧。根据这些数据，我们提出了 Lass 家族成员中保守的 Lag1 基序的拓扑结构，即 N 端区域面向内质网膜的腔侧，C 端区域面向内质网膜的细胞质侧。

  DOI：

  10.1042/bj20050291

文献信息

• Loss of ceramide synthase 3 causes lethal skin barrier disruption
  作者：Richard Jennemann、Mariona Rabionet、Karin Gorgas、Sharon Epstein、Alexander Dalpke、Ulrike Rothermel、Aline Bayerle、Franciscus van der Hoeven、Silke Imgrund、Joachim Kirsch、Walter Nickel、Klaus Willecke、Howard Riezman、Hermann-Josef Gröne、Roger Sandhoff

  DOI：10.1093/hmg/ddr494

  日期：2012.2.1

  The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1–6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (≥C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage.

  作为最外层表皮层的角质层可防止干燥和感染。 角质层下角质包膜（CE）和细胞间脂质基质是这两层主要保护屏障的主要组成部分。 表皮特有的具有超长链酰基（ULC-Cer）的神经酰胺是细胞外脂质层（ELL）的关键组成部分，并与CE蛋白结合，从而形成角质脂质包膜（CLE）。 在这里，我们确定了人类和鼠神经酰胺合成酶3（CerS3），在CerS1-6中，CerS3是体外ULC-Cer合成和体内小鼠CerS3合成的唯一必需成分。 小鼠CerS3的缺乏会导致ULC-Cer（≥C26）的完全丧失，缺乏连续的ELL和无法发挥功能的CLE。 因此，新生突变小鼠在出生后不久就会因表皮水分流失而死亡。 突变皮肤容易感染白色念珠菌，这表明ULC-Cer对于这两种屏障功能至关重要。 持续性外皮、角化过度和角质化不足是突变皮肤的特征，表明神经酰胺的丧失会导致角质形成细胞在胚胎屏障前阶段成熟停滞。
• Characterization of Ceramide Synthase 2
  作者：Elad L. Laviad、Lee Albee、Irene Pankova-Kholmyansky、Sharon Epstein、Hyejung Park、Alfred H. Merrill、Anthony H. Futerman

  DOI：10.1074/jbc.m707386200

  日期：2008.2

  CoAs (C20-C26) for ceramide synthesis. There is a good correlation between CerS2 mRNA levels and levels of ceramide and sphingomyelin containing long acyl chains, at least in tissues where CerS2 mRNA is expressed at high levels. Interestingly, the activity of CerS2 can be regulated by another bioactive sphingolipid, sphingosine 1-phosphate (S1P), via interaction of S1P with two residues that are part

  神经酰胺是重要的脂质信号分子，是鞘脂生物合成中的关键中间体。最近的研究暗示了神经酰胺N-酰基链长的作用是前所未有的，因为含有特定脂肪酸的神经酰胺似乎在细胞生理学中起着确定的作用。哺乳动物神经酰胺合酶（CerS）家族的发现加强了这一观念，每个家族都利用酰基辅酶A的一个有限子集进行神经酰胺合成。现在，我们报告哺乳动物CerS2的表征。qPCR分析表明，在所有CerS中，CerS2 mRNA的含量最高，并且组织分布最广。CerS2具有出色的酰基CoA特异性，使用C16：0-CoA时无活性，而使用C18：0则显示低活性，而是利用更长的酰基链CoA（C20-C26）进行神经酰胺合成。至少在高水平表达CerS2 mRNA的组织中，CerS2 mRNA水平与含有长酰基链的神经酰胺和鞘磷脂水平之间存在良好的相关性。有趣的是，CerS2的活性可以通过另一种生物活性鞘脂，1-磷酸鞘氨醇（S1P）来调节，这是通
• C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p
  作者：I. Guillas

  DOI：10.1093/emboj/20.11.2655

  日期：2001.6.1

  Lag1p and Lac1p are two highly homologous membrane proteins of the endoplasmic reticulum (ER). When both genes are deleted, cells cannot transport glycosylphosphatidylinositol (GPI)-anchored proteins from the ER to the Golgi at a normal rate. Here we show that microsomes or detergent extracts from lag1 Delta lac1 Delta double mutants lack an activity transferring C26 fatty acids from C26-coenzyme A onto dihgdrosphingosine or phytosphingosine. As a consequence, in intact cells, the normal ceramides and inositolphosphorylceramides are drastically reduced. lag1 Delta lacl Delta cells compensate for the lack of normal sphingolipids by making increased amounts of C26 fatty acids, which become incorporated into glycerophospholipids. They also contain 20- to 25-fold more free long chain bases than wild type and accumulate very large amounts of abnormally polar ceramides, They make small amounts of abnormal mild base-resistant inositolphospholipids. The lipid remodelling of GPI-anchored proteins is severely compromised in lag1 Delta lac1 Delta double mutants since only few and mostly abnormal ceramides are incorporated into the GPI anchors. The participation of Lag1p and Lac1p in ceramide synthesis may explain their role in determining longevity.
• Human Homologues of LAG1 Reconstitute Acyl-CoA-dependent Ceramide Synthesis in Yeast
  作者：Isabelle Guillas、James C. Jiang、Christine Vionnet、Carole Roubaty、Danièle Uldry、Rachel Chuard、Jinqing Wang、S.Michal Jazwinski、Andreas Conzelmann

  DOI：10.1074/jbc.m307554200

  日期：2003.9

  Lag1p and Lac1p are two highly homologous membrane proteins of the endoplasmic reticulum. lag1Delta lac1Delta double mutants in Saccharomyces cerevisiae lack an acyl-CoA-dependent ceramide synthase and are either very sick or nonviable, depending on the genetic background. LAG1 and LAC1 are members of a large eukaryotic gene family that shares the Lag1 motif, and some members of this family additionally contain a DNA-binding HOX homeodomain. Here we show that several human LAG1 homologues can rescue the viability of lag1Delta lac1Delta yeast cells and restore acyl-CoA-dependent ceramide and sphingolipid biosynthesis. When tested in a microsomal assay, Lac1p and Lag1p had a strong preference for C26:0-CoA over C24:0-CoA, C20-CoA, and C16-CoA, whereas some human homologues preferred C24:0-CoA and CoA derivatives with shorter fatty acids. This suggests that LAG1 proteins are related to substrate recognition and to the catalytic activity of ceramide synthase enzymes. CLN8, another human LAG1 homologue implicated in ceroid lipofuscinosis, could not restore viability to lag1Delta lac1Delta yeast mutants.
• Lip1p: a novel subunit of acyl-CoA ceramide synthase
  作者：Béatrice Vallée、Howard Riezman

  DOI：10.1038/sj.emboj.7600562

  日期：2005.2.23

  Ceramide plays a crucial role as a basic building block of sphingolipids, but also as a signalling molecule mediating the fate of the cell. Although Lac1p and Lag1p have been shown recently to be involved in acyl- CoA- dependent ceramide synthesis, ceramide synthase is still poorly characterized. In this study, we expressed tagged versions of Lac1p and Lag1p and purified them to near homogeneity. They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. In purified form, the acyl- CoA dependence, fatty acyl- CoA chain length specificity, and Fumonisin B1/ Australifungin sensitivity of the ceramide synthase were the same as in cells, showing that these are properties of the enzyme and do not depend upon the membrane environment or other factors. SDS - PAGE analysis of purified ceramide synthase revealed the presence of a novel subunit of the enzyme, Lip1p. Lip1p is a single- span ER membrane protein that is required for ceramide synthesis in vivo and in vitro. The Lip1p regions required for ceramide synthesis are localized within the ER membrane or lumen.