PHYSICO-CHEMICAL REGULATN OF ENZYMES IN LIPID METABOLISM

这个项目的目标是确定 来自胰腺的磷脂酶A2和脂酶依赖性脂肪酶 在脂水相界进行调节。据推测，一个 这种调节的主要因素是体内脂质的横向组织。 脂水界面的平面。这样的规定是明示的 在酶从水溶液分配到界面的水平上 溶液和界面内的催化水平。 重点是了解脂质成分、包装、 表面电势与启动过程中的蛋白质辅因子--乳脂酶 和维持磷脂酰胆碱和甘油三酯的水解，即， (磷酸)脂解作用。 确定组织影响的程度 模型中的(磷)脂解、酶吸附和催化 将测量磷脂-甘油三酯的界面。这将包括 初始速度测量和测量范围 吸附和催化作用。界面将是单层的，并且 脂类成分受到高度控制的双分子层， 堆积密度和电学性能。通过更正以下各项的结果 常见的酶和酶的强度变量的贡献 底物浓度，组织依赖的影响将是 被揭露了。当根据脂质成分进行检查时，这些校正 数据将揭示假设的关键 转变的发生以及相对脂团大小如何随着 对临界成分进行了探讨。在相关实验中，平均 将测量集群大小。 这些研究针对的是界面反应的调节， 不仅发生在肠道，而且发生在所有组织中。这样的反应是 参与炎症过程、脂质转运和信号传递 转导。他们的控制或缺乏控制，导致了 动脉粥样硬化和关节炎等疾病的病理学。

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.