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THE METABOLISM AND FUNCTION OF THE POLYPRENOLS

聚戊烯醇的代谢和功能

基本信息

批准号：
3151100
负责人：
ROY W KEENAN
金额：
$ 7.43万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-06-01 至 1986-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3151100
关键词：
biological models carbohydrate metabolism cofactor diet high performance liquid chromatography isoprenoid lipid metabolism membrane structure nutrition related tag phosphorylation radiotracer

项目摘要

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.

糖蛋白是一类非常大的蛋白质，具有许多不同的功能。这些蛋白质中的大多数是通过添加共同的或 “核心”寡糖链到蛋白质中的天冬酰胺。碳水化合物该分子的一部分然后通过移除和添加不同的加糖，直到形成合适的化合物。拟议的研究具有以下特点它的目标是收集数据，使我们能够理解 “核心”低聚糖的组装以及它最终是如何转移到蛋白。众所周知，这个过程涉及一系列反应，在这些反应中，碳水化合物中间体连接到顺式聚异戊二烯基磷酸酯或焦磷酸盐。这类化合物被称为二羟基苯酚，它消除了对糖蛋白代谢有浓厚的兴趣，对此知之甚少这些关键中间体的新陈代谢。这项提案中的实验是继续我们对生物合成、磷酸化、去磷酸化、细胞和亚细胞的分布、储存和排泄一种多效酚。此外，二烷基二酚作为一种糖蛋白生物合成的中间体也将被研究。这些实验涉及放射性多元醇的化学合成。以及类似衣霉素的化合物抑制糖蛋白生物合成。这些化合物将被用作工具来帮助我们剖析糖蛋白整个过程中的个别反应生物合成，以便对它们进行研究。糖尿病是一种严重后果之一的疾病异常膜结构的发展可能是由于产生异常糖蛋白。实验将在以下情况下进行链脲佐菌素诱导的糖尿病动物研究是否会发生深刻的变化这种疾病产生的碳水化合物和脂肪代谢对在多醇介导的糖蛋白合成中的反应最终导致异常糖蛋白的产生。