Elucidation of the synthetic mechanism, disorders, and physiological functions of very long-chain fatty acids

虽然碳链长度大于20 （>C20）的甚长链脂肪酸（VLCFAs）的细胞含量比长链脂肪酸（LCFAs; C11-C20）少，但VLCFAs具有LCFAs无法替代的重要功能，并与一些疾病有关。本课题通过敲除小鼠和培养细胞的生理和细胞生物学分析，揭示了VLCFAs在皮肤屏障形成中的功能，VLCFAs代谢与肾上腺素营养不良、肌病、智力低下等多种疾病的关系，神经酰胺合成酶对VLCFAs合成酶的调节机制，VLCFAs在核内体囊泡运输中的作用。用纯化的VLCFA合成酶和酵母遗传学方法进行生化分析。

Although cellular level of very long-chain fatty acids (VLCFAs), which have carbon chain-length greater than 20 (>C20), is less abundant than that of long-chain fatty acids (LCFAs; C11-C20), VLCFAs possess important functions that cannot be substituted for by LCFAs and related to some disorders. In this research project, we revealed the functions of VLCFAs in skin barrier formation, relationship between metabolism of VLCFAs and several disorders such as adrenoleucodystrophy, myopathy, and mental retardation, regulatory mechanism of the VLCFA synthetic enzymes by the ceramide synthases, and the roles of VLCFAs in the vesicular transport via endosomes, by physiological and cell biological analyses using knockout mice and cultured cells, by biochemical assays using purified VLCFA synthetic enzymes, and by yeast genetical approach.