KINETICS OF PLASMA LIPOPROTEIN ASSEMBLY AND SECRETION

血浆脂蛋白组装和分泌的动力学

• 批准号: 3349412
• 负责人: ROBERT D PHAIR
• 金额: $ 5.75万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349412
• 关键词: apolipoproteins; biological models; blood lipoprotein biosynthesis; blood lipoprotein metabolism; calcium metabolism; cell free system; chemical reaction; chickens; cholesterol; computer simulation; liver cells; liver metabolism; oligosaccharides; phosphatidylinositols; phosphatidylserines; radiotracer; tissue /cell culture; tritium; very low density lipoprotein

Although kinetic analysis has contributed many advances to the field of plasma lipoprotein metabolism, it has been applied at the level of whole animal or whole human physiology almost exclusively. With the advent of modern biochemical and cell culture techniques it has become feasible to employ kinetic modeling methods in the study of intracellular and organellar processes. This project is designed to test current theories concerning hepatic assembly and secretion of very low density lipoproteins (VLDL) and, where necessary, to propose and test modifications of these theories. We will employ estrogenized chick hepatocytes in short-term monolayer culture and a newly developed (hepatocyte-derived) cell-free system as our experimental model systems; kinetic data from both published and planned experiments using glycerolipid, cholesterol, apoprotein and oligosaccharide tracers will permit detailed quantitative tests of current paradigms. This testing will be done by expressing a proposed theory as a kinetic model and comparing its predictions to our experimental data using the SAAM and CONSAM computer programs. Finally, intracellular metabolite fluxes and compartmental contents will be calculated based on the tracer data and associated mass measurements.

尽管动力学分析为领域做出了许多进步 血浆脂蛋白代谢，已在整个水平上应用 动物或整个人类生理学几乎完全。 随着出现 现代化的生化和细胞培养技术已变得可行 在细胞内和 细胞器过程。 该项目旨在测试当前理论 关于肝组装和非常低密度脂蛋白的分泌 （VLDL），并且在必要时提出和测试这些修改 理论。 我们将在短期内采用雌激素化的鸡肝细胞 单层培养物和新开发的（肝细胞衍生的）无细胞 系统作为我们的实验模型系统；两者都发表的动力学数据 并计划使用甘油，胆固醇，载脂蛋白和 寡糖示踪剂将允许对电流进行详细的定量测试 范式。 该测试将通过表达提出的理论作为一个 动力学模型并使用其预测与我们的实验数据进行比较 SAAM和COSSAM计算机程序。 最后，细胞内代谢产物 将根据示踪剂计算通量和隔室内容 数据和相关的质量测量。