BRAIN GLYCOLIPIDS: METABOLISM AND PATHOLOGY

激活三种鞘脂水解酶的一组蛋白质 (葡萄糖脑苷酶、半乳糖脑苷酶和鞘磷脂酶) 深入研究。我们将开发一种免疫分析方法来测量它们的 在不同脑细胞类型和亚细胞组分中的浓度， 器官和体液。这些浓度随年龄的变化 和生理状态，包括神经鞘脂的遗传性疾病 新陈代谢，将进行测量，以努力阐明它们的功能。 该抗体还将用于制备和免疫亲和柱，作为 帮助大规模分离激活剂。化学研究将 用激活剂来测定它们的氨基酸序列，并 确定激活酶所需的区域。这也许是可能的 使用激活剂作为酶的稳定剂，以提高酶的稳定性 酶疗法对这些疾病(尤其是高雪病)的疗效 疾病)。 类似的研究将对帮助转移的蛋白质进行 膜间脑苷脂。我们将努力做好主动降解的准备 蛋白质的产物，也看看蛋白质是否刺激了这种行为 各种糖类合成酶。 脑鞘磷脂变化的进一步研究 将会进行禁食。我们将调查这一水平是否可能 大脑中游离脂肪酸的含量控制着神经酰胺的水平。 将在脑膜部分进行酶研究，看看是否 合成神经酰胺确实有五种酶。身份识别 将尝试在大脑中合成鞘磷脂的途径。 一种新的视频密度计在脂肪分析中的价值将被确定。

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.