THE METABOLISM AND FUNCTION OF THE POLYPRENOLS

糖蛋白是一类非常大的蛋白质，具有许多不同的结构。 功能协调发展的 这些蛋白质中的大多数是通过添加常见或 在蛋白质中，“核心”寡糖链与天冬酰胺连接。 碳水化合物 然后通过去除和添加各种修饰剂来修饰该分子的一部分。 糖直到形成合适的化合物。 拟议的研究作为 其目标是收集数据，使我们能够了解 组装的“核心”寡糖，以及它是如何最终转移到 蛋白 已知该过程涉及一系列反应，其中 碳水化合物中间体连接到顺式聚异戊二烯磷酸盐或 焦磷酸盐 这类化合物被称为多萜醇， 对糖蛋白代谢的强烈兴趣，相对而言， 这些关键中间体的代谢。 该提案中的实验是 我们对生物合成，磷酸化， 去磷酸化、细胞和亚细胞分布、储存和排泄 关于Dolichol 此外，还研究了其中长萜醇作为 还将研究糖蛋白生物合成中的中间体。 这些实验涉及放射性多萜醇的化学合成 类似于衣霉素的衍生物和化合物 糖蛋白生物合成 这些化合物将被用作帮助我们 剖析糖蛋白合成过程中的各个反应 生物合成，以便进行研究。 糖尿病是一种疾病，其严重后果之一是， 异常膜结构的发展，可能是由于 异常糖蛋白的产生。 实验将进行与 动物与链脲佐菌素诱导的糖尿病，看看是否深刻的变化， 这种疾病产生的碳水化合物和脂质代谢对 反应中的Dolichol介导的糖蛋白的合成，最终 导致产生异常糖蛋白。

Glycoproteins are a very large class of proteins that have many diverse functions. Most of these proteins are assembled by the addition of a common or "core" oligosaccharide chain to an asparagine in the protein. The carbohydrate portion of this molecule is then modified by the removal and addition of various sugars until the appropriate compound is formed. The proposed research has as its objectives the collection of data that will enable us to understand the assembly of the "core" oligosaccharide and how it is eventually transferred to protein. This process is known to involve a series of reactions in which the carbohydrate intermediates are linked to cis-polyisoprenyl phosphates or pyrophosphates. This class of compound is called dolichol and, dispite the intense interest in glycoprotein metabolism, relatively little is known about the metabolism of these key intermediates. The experiments in this proposal are a continuation of our studies on the biosynthesis, phosphorylation, dephosphorylation, cellular and subcellular distribution, storage and excretion of dolichol. In addition, the reactions in which dolichol serves as an intermediate in the biosynthesis of glycoproteins will also be investigated. These experiments involve the chemical synthesis of radioactive dolichol derivatives as well as compounds similar to tunicamycin which inhibit glycoprotein biosynthesis. These compounds will be used as tools to aid us in dissecting the individual reactions in the overall process of glycoprotein biosynthesis so that they can be studied. Diabetes is a disease which has as one of its serious consequences the development of abnormal membrane structures that probably result from the production of abnormal glycoproteins. Experiments will be conducted with animals with streptazotocin-induced diabetes to see if the profound changes in carbohydrate and lipid metabolism produced by this disease have effects on reactions in the dolichol-mediated synthesis of glycoproteins that ultimately result in abnormal glycoproteins being produced.