PHYSICOCHEMICAL ENZYME REGULATION IN LIPID METABOLISM

脂质代谢中的理化酶调节

• 批准号: 2225278
• 负责人: Howard L. Brockman
• 金额: $ 18.92万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2225278
• 关键词: PHYSICOCHEMICAL; ENZYME; REGULATION; LIPID; METABOLISM

The goal of this project is to determine the mechanisms by which the phospholipase A2 and colipase-dependent lipase from pancreas are regulated at lipid-water phase boundaries. It is hypothesized that a major factor in this regulation is the lateral organization of lipids in the plane of the lipid-water interface. Such regulation is expressed both at the level of enzyme partitioning to the interface from aqueous solution and at the level of catalysis within the interfacial plane. Emphasis is on understanding the roles of lipid composition, packing, surface potential and the protein cofactor, colipase, in the initiation and maintenance of phosphatidylcholine and glyceride hydrolysis, i.e., (phospho) lipolysis. To identify the extent to which organization influences (phospho)lipolysis, enzyme adsorption to and catalysis in model phospholipid-glyceride interfaces will be measured. This will include both initial rate measurements and measurement of the extent of adsorption and catalysis. The interfaces will be monolayers and bilayers which are highly controlled with respect to lipid composition, packing density and electrical properties. By correcting results for the contribution of the usual intensive variables of enzyme and substrate concentrations, organization-dependent effects will be revealed. When examined on a lipid composition basis, these corrected data will reveal the composition at which the postulated critical transition occurs and how relative lipid cluster size changes as the critical composition is approached. In related experiments, average cluster size will be measured. These studies address the regulation of interfacial reactions which occur not only in the intestine but in all tissues. Such reactions are involved in inflammatory processes, lipid transport and signal transduction. Their control, or lack of it, contributes to the pathology of diseases such as atherosclerosis and arthritis.

该项目的目标是确定机制 来自胰腺的磷脂酶 A2 和辅脂肪酶依赖性脂肪酶 在脂质-水相边界处进行调节。 假设一个 这种调节的主要因素是脂质的横向组织 脂质-水界面的平面。 这样的规定是这样表达的 两者都在酶从水分配到界面的水平上 溶液和界面平面内的催化水平。 重点是了解脂质成分、堆积、 表面电位和蛋白质辅因子辅脂肪酶在起始过程中 和维持磷脂酰胆碱和甘油酯水解，即 （磷酸）脂肪分解。 确定组织影响的程度 模型中的（磷酸）脂肪分解、酶吸附和催化 将测量磷脂-甘油酯界面。 这将包括 初始速率测量和程度测量 吸附和催化。 界面将是单层的并且 脂质成分受到高度控制的双层， 堆积密度和电性能。 通过修正结果 酶的通常强度变量的贡献和 底物浓度，组织依赖性效应将是 揭示了。 当根据脂质成分进行检查时，这些校正 数据将揭示假设的临界值的成分 转变发生以及相对脂质簇大小如何随着 接近临界构图。 在相关实验中，平均 将测量簇大小。 这些研究涉及界面反应的调节 不仅发生在肠道，而且发生在所有组织中。 此类反应是 参与炎症过程、脂质转运和信号 转导。 他们的控制或缺乏控制会导致 动脉粥样硬化和关节炎等疾病的病理学。