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BRAIN GLYCOLIPIDS: METABOLISM AND PATHOLOGY

脑糖脂：代谢和病理学

基本信息

批准号：
3393285
负责人：
NORMAN S. RADIN
金额：
$ 14.43万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-02-01 至 1992-01-31
项目状态：
已结题

项目摘要

The group of proteins which activate three sphingolipid hydrolases (glucocerebrosidase, galatocerebrosidase, and sphingomyelinase) will be studied in depth. We will develop an immunoassay for measuring their concentration in different brain cell types and subcellular fractions, organs, and fluids. Changes in these concentrations as a function of age and physiological state, including genetic disorders of sphingolipid metabolism, will be measured in an effort to elucidate their functions. The antibodies will also be used to prepare and immunoaffinity column as an aid in the large-scale isolationof the activators. Chemical studies will be made with the activaters to determine their amino acid sequences and to identify the regions needed for activating the enzymes. It may be possible to use the activators as stabilizers of the enzymes in order to improve the effeciveness of enzyme therapy of the disorders (especially Gaucher disease). Similar studies will be made of the proteins which aid in the transfer of cerebrosides between membranes. We will try to prepare active degradation products of the proteins and also see if the proteins stimulate the action of various glycopid synthetases. Further study of the changes in brain sphingolipids that are produced by fasting will be done. We will investigate the possibility that the level of free fatty acids in brain controls the level of ceramide. Enzyme studies will be carried out in brain membrane fractions to see if there are indeed five enzymes for synthesizing ceramide. Identification of the pathway for sphingomyelin synthesis in brain will be attempted. The value of a new video densitometer in lipid analysis will be determined.

激活三种鞘脂水解酶的蛋白质组（葡萄糖脑苷脂酶、半乳糖脑苷脂酶和鞘磷脂酶）将深入研究。我们将开发一种免疫测定法来测量它们不同脑细胞类型和亚细胞部分的浓度，器官和体液。这些浓度随年龄的变化和生理状态，包括鞘脂遗传性疾病新陈代谢，将被测量以努力阐明它们的功能。该抗体还将用于制备免疫亲和柱作为有助于大规模分离活化剂。化学研究将与激活剂一起制备以确定其氨基酸序列并确定激活酶所需的区域。或许有可能使用激活剂作为酶的稳定剂，以提高酶的活性酶疗法对疾病（尤其是戈谢病）的有效性疾病）。将对有助于转移的蛋白质进行类似的研究膜之间的脑苷脂。我们将尽力准备主动降解蛋白质的产物，并查看蛋白质是否刺激作用各种糖苷合成酶。进一步研究大脑产生的鞘脂的变化禁食将会完成。我们将调查该级别的可能性大脑中游离脂肪酸的含量控制着神经酰胺的水平。将在脑膜部分中进行酶研究，看看是否确实有五种酶可以合成神经酰胺。鉴定将尝试大脑中鞘磷脂的合成途径。新型视频密度计在脂质分析中的价值将被确定。