Sandhoff K, Kolter T, Van Echten-Deckert G
Kekulé-Institut für Organische Chemie und Biochemie der Universität, Bonn, Germany.
Ann N Y Acad Sci. 1998 Jun 19;845:139-51. doi: 10.1111/j.1749-6632.1998.tb09667.x.
Sphingolipid metabolism and function was investigated using sphingoid analogs, cells from human sphingolipidoses patients, and knockout animals. Treatment of primary cultured murine cerebellar cells with the structurally modified sphingosine base cis-4 methylsphingosine resulted in decreased sphingolipid biosynthesis accompanied by significant morphological changes. Plasma-membrane-derived glycosphingolipids (GSLs) destined for digestion are internalized through the endocytic pathway and delivered to lysosomes. There, GSLs are degraded by the action of exohydrolases, which are supported, in the case of GSLs with short oligosaccharide chains, by sphingolipid activator proteins (SAPs or saposins). The inherited deficiency of activators give rise to sphingolipid storage diseases. The analysis of cultured fibroblasts from corresponding patients suggests a new model for the topology of endocytosis and lysosomal digestion. Mice with disrupted genes for activator proteins and for GM2 degrading hexosaminidases turned out to be useful models for human diseases.
利用鞘氨醇类似物、来自人类鞘脂贮积症患者的细胞以及基因敲除动物，对鞘脂代谢和功能进行了研究。用结构修饰的鞘氨醇碱基顺式-4-甲基鞘氨醇处理原代培养的小鼠小脑细胞，导致鞘脂生物合成减少，并伴有明显的形态学变化。 destined for digestion are internalized through the endocytic pathway and delivered to lysosomes. There, GSLs are degraded by the action of exohydrolases, which are supported, in the case of GSLs with short oligosaccharide chains, by sphingolipid activator proteins (SAPs or saposins). The inherited deficiency of activators give rise to sphingolipid storage diseases. The analysis of cultured fibroblasts from corresponding patients suggests a new model for the topology of endocytosis and lysosomal digestion. Mice with disrupted genes for activator proteins and for GM2 degrading hexosaminidases turned out to be useful models for human diseases. 源自质膜的糖鞘脂（GSLs）通过内吞途径内化并传递到溶酶体。在那里，GSLs在外切水解酶的作用下被降解，对于具有短寡糖链的GSLs，鞘脂激活蛋白（SAPs或鞘磷脂激活蛋白）会提供支持。激活剂的遗传性缺乏会导致鞘脂贮积病。对相应患者培养的成纤维细胞的分析提出了一种关于内吞作用拓扑结构和溶酶体消化的新模型。激活蛋白基因和GM2降解己糖胺酶基因被破坏的小鼠被证明是人类疾病的有用模型。 （原文中“Plasma-membrane-derived glycosphingolipids (GSLs) destined for digestion are internalized through the endocytic pathway and delivered to lysosomes.”一句翻译时出现部分重复，推测原文可能存在表述问题，已按正常理解翻译。）
