KINETICS OF PLASMA LIPOPROTEIN ASSEMBLY AND SECRETION

尽管动力学分析对动力学领域做出了许多贡献， 血浆脂蛋白代谢，它已被应用于整体水平， 动物或整个人类生理几乎完全。 的到来 现代生物化学和细胞培养技术， 采用动力学建模方法在细胞内的研究， 细胞器突起 这个项目是为了测试当前的理论 关于极低密度脂蛋白的肝组装和分泌 （VLDL），并在必要时提出和测试这些修改 理论 我们将在短期内使用雌激素化的鸡肝细胞 单层培养和新开发的（肝细胞衍生的）无细胞 系统作为我们的实验模型系统;动力学数据来自两个已发表的 和计划的实验，使用甘油脂质，胆固醇，载脂蛋白和 寡糖示踪剂将允许详细的定量测试电流 范例 该测试将通过将所提出的理论表示为 动力学模型，并将其预测与我们的实验数据进行比较， SAAM和CONSAM计算机程序。 最后，细胞内代谢物 将根据示踪剂计算通量和隔室含量 数据和相关的质量测量。

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.