REGULATORY ENZYMES IN PARASITIC HELMINTHS

寄生蠕虫中的调节酶

• 批准号: 3126685
• 负责人: TAG E. MANSOUR
• 金额: $ 23.91万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3126685
• 关键词: 6 phosphofructokinase; Schistosoma mansoni; adenylate cyclase; affinity chromatography; carbohydrate metabolism; cyclic AMP; enzyme mechanism; enzyme structure; enzyme substrate; host organism interaction; phosphodiesterases; protein kinase; radiotracer; scintillation counter; serotonin; tissue /cell culture

The overall objective of this research is to gain better understanding of serotonin-activated adenylate cyclase and enzymes that are regulated by cyclic AMP in trematodes. We plan to use Fasciola hepatica to study the cyclase system in depth. We will solubilize, purify, and characterize the serotonin receptors and the GTP-regulatory protein component of the cyclase. We plan to characterize and isolate the substrate(s) of cyclic AMP-dependent protein kinase from Fasciola. This includes phosphofructokinase (PFK) which has just been purified in our laboratory. We will study the control of fluke PFK through phosphorylation, and the relationship between PFK structure and its function to meet the metabolic needs of the parasite. We will continue with our investigation on the nature of serotonin activated adenylate cyclase from Schistosoma mansoni. Some characterization studies will be done on the serotonin receptors to see how related they are to the Fasciola enzyme. We plan to identify serotonin analogs that act as agonists or antagonists on these receptors in adult schistosomes and in schistosomules, and examine their effect on development of the parasites. We will test the possiblity that serotonin antagonists can adversely affect adult schistosomes or schistosomules in vitro as well as in the host. One essential theme that runs through our research is identification of the differences as well as the similarities of properties of these enzymes and receptors in parasite and host. Our ultimate goal is to identify sites in the parasite that are amenable to pharmacological manipulation without affecting the host.

这项研究的总体目的是更好地了解 5-羟色胺激活的腺苷酸环化酶和酶受到调节的调节 循环放大器中的弹药。 我们计划使用fasciola hepatica研究 循环酶系统深入。 我们将溶解，净化和表征 5-羟色胺受体和GTP调节蛋白成分 循环酶。 我们计划表征和分离循环的底物 来自fasciola的AMP依赖性蛋白激酶。 这包括 刚刚在我们的实验室中纯化的磷酸果糖激酶（PFK）。 我们将通过磷酸化研究Fluke PFK的控制，并研究 PFK结构及其功能之间的关系以满足代谢 寄生虫的需求。 我们将继续对 5-羟色胺激活的腺苷酸环化酶的性质。 一些表征研究将在5-羟色胺受体上进行 查看它们与fasciola酶的关系。 我们计划确定 在这些受体上充当激动剂或拮抗剂的5-羟色胺类似物 成人血块和血吸虫中，并检查其对 寄生虫的发展。 我们将测试5-羟色胺的可能性 拮抗剂可能会对成人血统或血吸虫的影响不利 体外和宿主。 通过我们的一个基本主题 研究是识别差异和相似之处 这些酶和受体在寄生虫和宿主中的特性。 我们的 最终目标是识别寄生虫中的地点 药理学操纵而不会影响宿主。