LIPID TRANSPORT

这项研究计划的长期目标是调查 目前关于完整动物和分离细胞中脂类转运的概念 以及亚细胞组件之间。过量脂肪在人体内的沉积 组织伴随着导致疾病的细胞功能障碍。 比如动脉粥样硬化。我们打算在三点继续目前的工作。 水平：1)研究细胞膜中的膜脂组织和 改变膜脂成分的方法及其对血管紧张素系统的影响 膜结合酶，2)饮食引起的机制 高脂血症动物，以及3)胆固醇被 从肠道吸收的。未来的研究将包括尝试改变 首先使用脂转移蛋白的膜脂成分 在我们的实验室中被识别和隔离。将有可能改变 膜的脂肪酸饱和度和极性基团组成 并随后研究这些变化对酶的影响 例如腺酰环化酶、酰基辅酶A：胆固醇酰基转移酶和 以葡萄糖-6-磷酸酶为例。脂类替代对血管紧张性病变的影响 肠道细胞刷状边界准备将允许研究 肠内脂质转运现象对膜的依赖性 组成。在完整的兔子身上，我们将使用标记的胆固醇和 视黄醇，以测量这些脂质的吸收机制 肠道及其随后到血液的运输和各种 纸巾。脂蛋白、脂类和多肽分析与同位素联用 研究将被用来追踪血浆胆固醇的来源 高胆固醇和动物蛋白饲料喂养的兔。

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.