KINETICS OF PLASMA LIPOPROTEIN ASSEMBLY AND SECRETION

尽管动力学分析为该领域做出了许多进展 血浆脂蛋白代谢，已在整体水平上应用 几乎完全是动物或整个人类的生理学。随着……的到来 现代生化和细胞培养技术已经成为可行的 利用动力学建模方法研究细胞内和 细胞器突起。这个项目旨在检验当前的理论。 关于肝脏极低密度脂蛋白的组装和分泌 (极低密度脂蛋白)，并在必要时提出和测试对以下各项的修改 理论。我们将在短期内使用雌激素化的鸡肝细胞 单层培养和一种新开发的(肝细胞来源)无细胞 系统作为我们的实验模型系统；来自两个发表的动力学数据 并计划使用甘油脂、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 范例。这项测试将通过将提议的理论表达为 动力学模型，并将其预测与我们的实验数据进行了比较 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内容物 数据和相关质量测量。

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.