COORDINATION OF APOLIPOPROTEIN METABOLISM IN MAN

人类载脂蛋白代谢的协调

• 批准号: 3340492
• 负责人: WALDO R FISHER
• 金额: $ 19.42万
• 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/3340492
• 关键词: antihypercholesterolemic agent; apolipoproteins; blood lipoprotein metabolism; blood lipoprotein transport; chemical reaction; cholesterol; cholesterol esters; cholestyramine; diabetes mellitus; 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; tritium; 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.

这项研究是一项持续的动力学研究。 人类的载脂蛋白代谢。载脂蛋白是一种血浆介质 而这项研究关注的是 血浆脂质转运和载脂蛋白分泌到 血浆。 我们的研究有两个基本假设。1)我们建议 个体载脂蛋白的代谢是协调的，而且 系统功能响应于对等离子体传输的要求 单独的脂类。因此，我们将测量血浆分泌率 主要的载脂蛋白和甘油三酯、胆固醇及其酯 和磷脂，使用生物合成结合的示踪剂 H3-亮氨酸、H3-甲戊酸和C14-甘油。正常受试者和有 选定的高脂蛋白血症将在普通饮食中进行研究，并再次进行 在代谢紊乱后，通过胆固醇喂养，一种欧米茄-3脂肪酸 富含脂肪的饮食，给予胆碱胺或甲氧西林。这个 脱脂蛋白和脱脂蛋白的分泌速率常数和血浆转运测定 在这些不同的条件下，选择不同的血脂进行比较 深入了解载脂蛋白的调控机制 新陈代谢。 2)我们将研究apo B的分泌途径，包括 脂蛋白来记录分泌途径和 这些脂蛋白的物理异质性。我们建议在身体上 载脂蛋白B的异质性是由载脂蛋白B引起的 沿着进入不同脂蛋白种类的途径分泌，以及 载脂蛋白B在各个分泌途径上的转运幅度是 由这个要运输的脂类的量决定 载脂蛋白。这一假设将在相同的受试者中进行检验， 测定血脂转运率和载脂蛋白B分泌至极低密度脂蛋白、低密度脂蛋白 和分级的低密度脂蛋白亚种。 因此，这些研究将启动对这一关系的调查 载脂蛋白的产生与脂类存在的数量之间的关系 在等离子体中传输。