COORDINATION OF APOLIPOPROTEIN METABOLISM IN MAN

人类载脂蛋白代谢的协调

• 批准号: 3340490
• 负责人: WALDO R FISHER
• 金额: $ 18.66万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3340490
• 关键词: antihypercholesterolemic agent; apolipoproteins; blood lipoprotein metabolism; blood lipoprotein transport; chemical reaction; cholesterol; cholesterol esters; cholestyramine; familial hyperlipoproteinemia type II; fluorimetry; gel electrophoresis; high density lipoproteins; human subject; hypertriglyceridemia; leucine; lipid metabolism; lipid transport; lovastatin; low density lipoprotein; mevalonate; molecular pathology; phosphatidylcholines; radionuclide diagnosis; radiotracer; secretion; triglycerides; ultrafiltration; very low density lipoprotein

This research is a continuing investigation of the kinetics of apolipoprotein metabolism in humans. Apolipoproteins are plasma mediators of lipid transport, and this investigation concerns the relationship between plasma lipid transport and the secretion of apolipoproteins into plasma. Two general hypotheses underlie our studies. 1) We proposed that the matabolism of the individual apolipoproteins is coordinated and that the system functions in response to the requirements for plasma transport of individual lipids. Accordingly we shall measure the plasma secretory rates for the major apolipoproteins and for triglyceride, cholesterol, its esters and phospholipid, using biosynthetically incorporated tracers of H3-leucine, H3-mevalonate and C14-glycerol. Normal subjects and those with selected hyperlipoproteinemias will be studied on a common diet and again after metabolic perturbation, by cholesterol feeding, an Omega-3 fatty acid enriched fat diet, administration of cholestyramine or Mevinolin. The secretory rate constants and plasma transports measured for apoproteins and individual lipids will be compared under these various conditions, chosen to provide insight into control mechanisms regulating apolipoprotein metabolism. 2) We will examine the pathways for secretion of apo B containing lipoproteins to document relationships between secretory routes and physical heterogencity of these lipoproteins. We propose that physical heterogeneity within the apo B containing lipoproteins results from apo B secretion along pathways entering different lipoprotein species and that the magnitude of apo B transport over individual secretory pathways is determined by the amount of lipid to be transported by this apolipoprotein. This hypothesis will be examined in the same subjects, measuring plasma lipid transport rates and apo B secretion into VLDL, IDL and the fractionated LDL subspecies. These studies will thus initiate an investigation of the relationship between apolipoprotein production and the quantity of lipid being transported in plasma.

本研究是对以下动力学的持续研究： 人体载脂蛋白代谢。 载脂蛋白是血浆介质 脂质运输，这项调查涉及的关系， 血浆脂质转运和载脂蛋白分泌之间的关系 等离子体 我们的研究有两个基本假设。 1)我们建议 单个载脂蛋白的基质是协调的， 系统功能响应血浆运输的要求， 单个脂质。 因此，我们将测量血浆分泌率 主要载脂蛋白和甘油三酯、胆固醇及其酯 和磷脂，使用生物合成掺入的示踪剂， H3-亮氨酸、H3-甲羟戊酸和C14-甘油。 正常受试者和 选择高脂蛋白血症将在普通饮食下进行研究， 在代谢紊乱后，通过胆固醇喂养， 富含脂肪的饮食，给予消胆胺或Mevinolin。 的 分泌速率常数和血浆转运测定载脂蛋白和 将在这些不同的条件下比较各个脂质， 深入了解载脂蛋白的调控机制 新陈代谢. 2)我们将检查含有载脂蛋白B的分泌途径 脂蛋白来记录分泌途径和 这些脂蛋白的物理异质性。 我们建议， 载脂蛋白B导致含载脂蛋白B内的异质性 分泌沿着途径进入不同的脂蛋白种类， 载脂蛋白B通过单个分泌途径转运量是 这取决于要通过这种方式运输的脂质的量。 载脂蛋白 这一假设将在相同的受试者中进行检验， 测量血浆脂质转运率和apo B分泌到VLDL、IDL中 和低密度脂蛋白亚种。 因此，这些研究将启动对 载脂蛋白的产生和脂质的量之间的关系 用血浆运送