C8 beta-D-glucosyl N-acylsphingosine

• 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: C8 beta-D-glucosyl N-acylsphingosine
• 英文别名: 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]octanamide
• 化学式: C₃₂H₆₁NO₈
• 分子量: 587.8
• InChiKey: LCEXEEHGNKGJES-KHEBUCLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  41
• 可旋转键数：
  25
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 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 、 C8 beta-D-glucosyl N-acylsphingosine 生成 25-substituted-cholesteryl β-D-glucoside 、 N-辛酰基-D-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

文献信息

• 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.