LIPID TRANSPORT

本研究计划的长远目标是研究 完整动物、分离细胞中脂质转运的当前概念 以及亚细胞成分之间的联系。 多余的脂质沉积在 组织伴随着细胞功能障碍， 例如动脉粥样硬化。 我们打算继续目前的工作， 水平：1）研究细胞膜中的膜脂组织， 改变膜脂组成的方法及其对 膜结合酶，2）饮食引起的机制 高脂血症动物，和3）胆固醇的机制， 从肠道吸收。 未来的研究将包括尝试改变 首先通过使用脂质转移蛋白 在我们的实验室里被识别和分离出来。 有可能改变 膜的饱和度和极性基团组成 然后研究这些改变对酶的影响 如腺苷酸环化酶、酰基CoA：胆固醇酰基转移酶， 例如葡萄糖-6-磷酸酶。 脂质替代对 肠细胞刷状缘准备将允许研究 肠内脂质转运现象对膜的依赖性 混合物. 在完整的家兔中，我们将使用标记的胆固醇， 视黄醇，以测量这些脂质从 肠及其随后运输到血液和各种 组织中 脂蛋白脂质和多肽分析结合同位素 研究将被用来追踪血浆胆固醇的来源， 家兔接受高胆固醇和动物蛋白饮食。

The long-term objectives of this research proposal are to investigate current concepts of lipid transport in the intact animal, in isolated cells and between subcellular components. The deposition of excess lipid in tissues is accompanied by cellular malfunctions that result in diseases such as atherosclerosis. We intend to continue current work at three levels: 1) the study of membrane lipid organization in cell membranes and of methods to alter membrane lipid composition and its effect on membrane-bound enzymes, 2) the mechanisms whereby diet causes hyperlipidemia animals, and 3) the mechanisms whereby cholesterol is absorbed from the intestine. Future studies will include attempts to alter membrane lipid compositions by the use of lipid transfer proteins first recognized and isolated in our laboratory. It will be possible to alter the fally acid saturation as well as polar group composition of membrane lipids and subsequently study the effect of these alterations on enzymes such as adenyl cyclase, acylCoA:Cholesterol Acyltransferase and glucose-6-phosphatase as examples. The effects of lipid substitutions on intestinal cell brush border preparations will allow the study of dependence of lipid transport phenomena in the intestine on membrane composition. In the intact rabbit we will utilize labeled cholesterol and retinol to measure the mechanism of absorption of these lipids from the intestine and their subsequent transport to the bloodstream and various tissues. Lipoprotein lipid and polypeptide analysis coupled with isotopic studies will be employed to trace the origins of plasma cholesterol in rabbits subjected to high cholesterol and to animal protein diets.