[glucose-U]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sphingosine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 英文名称: [glucose-U]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sphingosine
• 英文别名: N-(2S,3R,E)-3-hydroxy-1-(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6(hydroxymethyl)(tetrahydro-2H-pyran-2-yl-oxy octadec-4-en-2-yl)stearamide；beta-D-glucosyl-N-octadecanoylsphingosine；N-[(E,2S,3R)-3-hydroxy-1-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadec-4-en-2-yl]octadecanamide
• 化学式: C₄₂H₈₁NO₈
• 分子量: 728.107
• InChiKey: YMYQEDCYNANIPI-DYJXBSQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.4
• 重原子数：
  51
• 可旋转键数：
  35
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  149
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  25-substituted-cholesterol 、 [glucose-U]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sphingosine 生成 25-substituted-cholesteryl β-D-glucoside 、 N-硬脂酰神经鞘氨醇
  参考文献：
  名称：

  Cholesterol glucosylation is catalyzed by transglucosylation reaction of β-glucosidase 1

  摘要：

  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.

  DOI：

  10.1016/j.bbrc.2013.10.145
• 作为产物：
  描述：

  4-硝基苯基硬脂酸酯 在 吡啶 、 4 A molecular sieve 、 三氟化硼乙醚 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 [glucose-U]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sphingosine
  参考文献：
  名称：

  Practical syntheses of [13C]- and [14C]-labelled glucosphingolipids

  摘要：

  本文描述了[葡萄糖-U-14C]-1-O-(β-D-吡喃葡萄糖基)-N-硬脂酰-D-赤藓-鞘氨醇 1b 和[葡萄糖-13C6]-1-O-(β-D-吡喃葡萄糖基)鞘氨醇 ([葡萄糖-13C6]葡萄糖鞘氨醇，2b) 的合成路线。虽然 1b 的受保护神经酰胺前体是用传统方法制备的，但在合成 2b 的过程中开发了两种新策略。其中一种方法是始终保持一个保护基团，以避免与鞘氨醇 4 相关的处理难题，而另一种方法则是通过三忍反转法间接生成鞘氨醇的保护衍生物 (24)。

  DOI：

  10.1039/b002104k

文献信息

• Total synthesis of ceramides and β-<i>O</i>-glucosylceramides <i>via</i> intramolecular fatty acyl group migration
  作者：Jaggaiah N. Gorantla、Maniganda Santhi、Yanling Hua、James R. Ketudat Cairns

  DOI：10.1039/d1nj05372h

  日期：——

  Acyl migration of alkyl and aromatic acyl groups from an alcohol to another alcohol or amine is a phenomenon that occurs in nature and can be a bane to some synthetic strategies. An acyl migration-dependent method was developed for the synthesis of ceramide and glucosyl ceramide derivatives, in which the desired fatty acyl moiety acts both as protecting and migrating group. Removal of the tetrachlorophthalimido

  烷基和芳香酰基从醇迁移到另一种醇或胺是自然界中发生的现象，可能是某些合成策略的祸根。开发了一种酰基迁移依赖性方法来合成神经酰胺和葡糖基神经酰胺衍生物，其中所需的脂肪酰基部分既充当保护基团又充当迁移基团。在室温下用乙二胺作为温和碱去除四氯邻苯二甲酰亚胺 (TCP) 基团导致随后的分子内脂肪酰基从 -O 迁移到 -N，在鞘氨醇或每个乙酰化葡糖基鞘氨醇上产生所需的N-酰化产物。脱乙酰化反应得到所需的 β- O-葡糖神经酰胺衍生物。因此，选择合适的封闭基团会将酰基迁移变成合成工具，而不是障碍。
• Klotho-related Protein Is a Novel Cytosolic Neutral β-Glycosylceramidase
  作者：Yasuhiro Hayashi、Nozomu Okino、Yoshimitsu Kakuta、Toshihide Shikanai、Motohiro Tani、Hisashi Narimatsu、Makoto Ito

  DOI：10.1074/jbc.m700832200

  日期：2007.10

  Using C6-NBD-glucosylceramide ( GlcCer) as a substrate, we detected the activity of a conduritol B epoxide-insensitive neutral glycosylceramidase in cytosolic fractions of zebrafish embryos, mouse and rat brains, and human fibroblasts. The candidates for the enzyme were assigned to the Klotho (KL), whose family members share a beta-glucosidase-like domain but whose natural substrates are unknown. Among this family, only the KL-related protein (KLrP) is capable of degrading C6-NBD-GlcCer when expressed in CHOP cells, in which Myc-tagged KLrP was exclusively distributed in the cytosol. In addition, knockdown of the endogenous KLrP by small interfering RNA increased the cellular level of GlcCer. The purified recombinant KLrP hydrolyzed 4-methylumbelliferyl-glucose, C6-NBD-GlcCer, and authentic GlcCer at pH 6.0. The enzyme also hydrolyzed the corresponding galactosyl derivatives, but each k(cat)/K-m was much lower than that for glucosyl derivatives. The x-ray structure of KLrP at 1.6 A resolution revealed that KLrP is a (beta/alpha) 8 TIM barrel, in which Glu(165) and Glu(373) at the carboxyl termini of beta-strands 4 and 7 could function as an acid/base catalyst and nucleophile, respectively. The substrate-binding cleft of the enzyme was occupied with palmitic acid and oleic acid when the recombinant protein was crystallized in a complex with glucose. GlcCer was found to fit well the cleft of the crystal structure of KLrP. Collectively, KLrP was identified as a cytosolic neutral glycosylceramidase that could be involved in a novel nonlysosomal catabolic pathway of GlcCer.
• Practical syntheses of [13C]- and [14C]-labelled glucosphingolipids
  作者：Gordon R. Duffin、George J. Ellames、Sascha Hartmann、John M. Herbert、David I. Smith

  DOI：10.1039/b002104k

  日期：——

  Synthetic routes to [glucose-U-14C]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sphingosine 1b and to [glucose-13C6]-1-O-(β-D-glucopyranosyl)sphingosine ([glucose-13C6]glucopsychosine, 2b) are described. Whereas the protected ceramide precursor for 1b was prepared using conventional methodology, two new strategies were developed in the course of the synthesis of 2b. Of these, one relies on keeping a protecting group in place at all times to avoid the handling difficulties associated with sphingosine 4, while the other generates a protected derivative (24) of sphingosine indirectly by means of a Mitsunobu inversion.

  本文描述了[葡萄糖-U-14C]-1-O-(β-D-吡喃葡萄糖基)-N-硬脂酰-D-赤藓-鞘氨醇 1b 和[葡萄糖-13C6]-1-O-(β-D-吡喃葡萄糖基)鞘氨醇 ([葡萄糖-13C6]葡萄糖鞘氨醇，2b) 的合成路线。虽然 1b 的受保护神经酰胺前体是用传统方法制备的，但在合成 2b 的过程中开发了两种新策略。其中一种方法是始终保持一个保护基团，以避免与鞘氨醇 4 相关的处理难题，而另一种方法则是通过三忍反转法间接生成鞘氨醇的保护衍生物 (24)。
• 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.