REGULATION OF HEPATIC CHOLESTEROL ESTER METABOLISM

肝脏胆固醇酯代谢的调节

• 批准号: 3237957
• 负责人: Sandra Karolyn Erickson
• 金额: $ 15.95万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237957
• 关键词: HMG coA reductases; acyl coA; acyltransferase; affinity labeling; antibody neutralization test; atherosclerosis; autoradiography; cholelithiasis; cholesterol; cholesterol esters; electrofocusing; enzyme biosynthesis; enzyme induction /repression; esterification; gel electrophoresis; homeostasis; immunoprecipitation; intestines; laboratory rabbit; laboratory rat; liver metabolism; membrane proteins; microsomes; molecular pathology; monoclonal antibody; phosphorylation; radiotracer; steroid metabolism; tissue /cell culture

The overall goal of the program is to elucidate the mechanisms of regulation of cholesterol homeostasis in the liver. Major emphasis is on the regulation of cholesterol esterification by the enzyme acyl coenzyme A: cholesterol acyltransferase (ACAT). This proposal is aimed at preparation of specific antibodies to ACAT in order to study the detailed regulation of this enzyme at the molecular, biochemical and physiological levels. Kinetic analyses of microsomal ACAT will be used to gain information on the relative importance of different modes of regulation of the enzyme. The antibodies will be used to examine regulation of ACAT by synthesis, degradation, phosphorylation; to investigate subcellular localization of ACAT in the liver and its localization in the intestine; and to study the molecular biology of the enzyme. These studies, by describing how cholesterol esterification in the liver is regulated, may help us to understand the pathologies of both atherosclerosis and cholelithiasis and may enable us to devise rational means of preventing or alleviating these diseases.

该计划的总体目标是阐明 肝脏胆固醇稳态的调节。 主要强调 是通过酶调节胆固醇酯化 酰基辅酶A：胆固醇酰基转移酶(ACAT)。 这 该提案旨在制备针对 ACAT 的特异性抗体 为了研究这种酶的详细调控 分子、生化和生理水平。 动力学分析 微粒体 ACAT 将用于获取有关 不同监管模式的相对重要性 酶。 这些抗体将用于检查调节 ACAT通过合成、降解、磷酸化；调查 ACAT在肝脏中的亚细胞定位及其定位 在肠道里；并研究分子生物学 酶。 这些研究通过描述胆固醇如何酯化 肝脏受到调节，可能有助于我们了解肝脏的病理学 动脉粥样硬化和胆石症，可能使我们能够设计 预防或减轻这些疾病的合理方法。