GLYCOSIDASES RELATED TO SPHINGOLIPIDOSES

与鞘脂相关的糖苷酶

• 批准号: 2261470
• 负责人: YU-TEH LI
• 金额: $ 32.5万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2261470
• 关键词: Annelida; Hirudinea; Krabbe's disease; Macaca mulatta; Tay Sachs disease; active sites; animal breeding; animal tissue; biotransformation; carbohydrate metabolism; ceramides; chemical group; cofactor; cow; disease /disorder model; enzyme mechanism; enzyme structure; enzyme substrate; exo alpha sialidase; glycolipids; glycoproteins; glycosidases; glycosphingolipids; human genetic material tag; human tissue; laboratory rabbit; laboratory rat; lipid metabolism; molecular cloning; molecular pathology; protein purification

Our long-term objectives continue to be the study of glycoconjugate catabolism toward the understanding of the molecular mechanism and pathogenesis of sphingolipidoses and allied disorders. Our knowledge of glycoconjugate catabolism has undergone several stages of evolution. Before the 1970s, it was believed that only exo- and endo-glycosidases were responsible for the degradation of complex carbohydrates. Today, we know that, in addition to glycosidases, activator proteins (protein cofactors) are also required for the degradation of sugar chains in glycosphingolipids (GSLs). The recent discovery of a ceramide glycanase which cleaves the linkage between the sugar chain and the lipid moiety of GSLs has further changed our concept on the catabolism of GSLs. For two decades, our laboratory has contributed to these developments. Our specific aims in this grant period can be divided into the following three categories. I. Catabolism of GSLs. In this series of investigation, we will focus on: (a) the isolation of GM2-activator from human placenta, cloning the gene encoding GM2-activator and studying the structure and the activation mechanism of this activator protein; (b) the study of the catabolism of GalCer, which includes the identification of the activator protein for the enzymatic hydrolysis of GalCer and development of an animal model for Krabbe's disease in rhesus monkeys. II. The study of two novel glycosidases. This work will focus on: (a) the studies of the specificity and biological significance of ceramide glycanase and its distribution in higher animals; (b) the investigation of the specificity, function and distribution of a novel sialidase which releases 2,7-anhydro-NeuAc from sialo-glycoconjugates; (c) the study of the biological function of 2,7-anhydro-NeuAc. III. A continuing search for new glycosidases and the exploration of better sources for glycosidases, activator proteins and glycoconjugate substrates. We believe that this research will contribute to a better understanding of the chemical pathology of storage diseases caused by the impaired degradation of glycoconjugates.

我们的长期目标继续是对糖缀合物的研究 对分子机制的理解的分解代谢 鞘脂和盟友的发病机理。 我们的知识 糖缀合物的分解代谢经历了几个进化阶段。 在1970年代之前，人们认为只有外糖苷和糖苷酶是 负责复杂碳水化合物的降解。 今天，我们知道 除糖苷酶外，激活蛋白（蛋白辅助因子）外 糖磷脂中的糖链降解也是必需的 （GSLS）。 最近发现的神经酰胺糖酶切割了 糖链和GSL的脂质部分之间的联系进一步 改变了我们对GSL的分解代谢的概念。 二十年来，我们 实验室为这些发展做出了贡献。 我们的具体目标 这个赠款期可以分为以下三个类别。 I. GSL的分解代谢。 在这一系列的调查中，我们将重点关注： （a）从人胎盘中分离GM2激活剂，克隆基因 编码GM2激活器并研究结构和激活 该激活蛋白的机制； （b）研究的研究代谢 Galcer，其中包括鉴定激活蛋白的 酶水的酶促水解和动物模型的发展 克拉布氏病在恒河猴中。 ii。 两种新型糖苷酶的研究。 这项工作将重点关注：（a） 关于神经酰胺的特异性和生物学意义的研究 糖酶及其在上等动物中的分布； （b）调查 新型唾液酸酶的特异性，功能和分布 从Sialo-GlyCoconjugates释放2,7-羟基NEUAC； （c）研究 2,7-Anhydro-Neuac的生物学功能。 iii。 继续寻找新的糖苷酶和探索 糖苷酶，激活蛋白和糖缀合物的更好来源 基材。 我们认为，这项研究将有助于更好地理解 储存疾病的化学病理因受损而引起 糖缀合物的降解。