神经酸甘油单酯 | 55030-84-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 中文名称: 神经酸甘油单酯
• 英文名称: glycerol mononervonate
• 英文别名: Mononervonin (15c)；2,3-dihydroxypropyl (Z)-tetracos-15-enoate
• CAS: 55030-84-7
• 化学式: C₂₇H₅₂O₄
• 分子量: 440.707
• InChiKey: NVQGQHXFWUBOAU-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  31
• 可旋转键数：
  25
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  神经酸甘油单酯 、 水 生成 (15Z)-tetracosenoate 、 甘油 、 氢(+1)阳离子
  参考文献：
  名称：

  Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids

  摘要：

  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.

  DOI：

  10.1074/jbc.ra118.005640
• 作为产物：
  描述：

  在 amberlyst-15 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 神经酸甘油单酯
  参考文献：
  名称：

  Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids

  摘要：

  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.

  DOI：

  10.1074/jbc.ra118.005640