BRAIN GLYCOLIPIDS: METABOLISM & PATHOLOGY

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）将被 深入研究。 我们将开发一种免疫测定法， 不同脑细胞类型和亚细胞级分中的浓度， 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 代谢，将被测量，以努力阐明其功能。 所述抗体还将用于制备免疫亲和柱，作为免疫亲和柱。 有助于活化剂的大规模分离。 化学研究将 用活化剂制备，以确定它们的氨基酸序列， 确定激活酶所需的区域。 有可能 使用活化剂作为酶的稳定剂，以改善酶的活性。 酶治疗疾病（尤其是高雪氏症）的有效性 疾病）。 类似的研究也将对帮助转移的蛋白质进行。 膜之间的间隙。 我们将尝试主动降解 并观察蛋白质是否刺激了 各种糖类合成酶的合成。 进一步研究脑鞘脂的变化， 将进行禁食。 我们会调查 大脑中游离脂肪酸的含量控制着神经酰胺的水平。 将在脑膜组分中进行酶研究，以观察 合成神经酰胺的酶确实有五种。 鉴定 将尝试脑中鞘磷脂合成的途径。 将确定一种新的视频密度计在脂质分析中的价值。

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.