FATTY ACID TRANSPORT AND TRANSFER PROTEINS

脂肪酸运输和转移蛋白

• 批准号: 3736266
• 负责人: Henry J. Pownall
• 金额: --
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736266
• 关键词: acylation; adipocytes; chemical transfer reaction; fatty acid transport; fibroblasts; free fatty acids; gas chromatography; hamsters; high density lipoproteins; immunocytochemistry; immunologic assay /test; lipid biosynthesis; liquid chromatography; low density lipoprotein; microscopy; peptide chemical synthesis; protein sequence; protein structure; proteins; transport proteins; triglycerides; very low density lipoprotein

Recent evidence suggests that abnormalities in the metabolism of triglycerides and fatty acids are linked to the occurrence of premature coronary artery disease. In cells, fatty acids are used as a source of energy, as building blocks for membrane biogenesis, and as precursors for complex regulatory molecules such as eicosanoids and thromboxanes. The transport of fatty acids among plasma and the many cellular compartments is a highly regulated process that is made all the more complex by postprandial lipemia and the attendant lipolysis. A major theme of the BCM-SCOR is that abnormalities in triglyceride and fatty acid metabolism contribute to atherosclerosis. Since elevation in fatty acids can contribute increased secretion of very low density lipoprotein- triglycerides, fatty acid and triglyceride metabolism are directly connected. Acylation-stimulating protein (ASP or BP-1) is one of three recently described proteins that promote the intracellular accumulation of fatty acids and their subsequent conversion of triglycerides, particularly in peripheral tissue. The role that this protein plays in abnormal lipid metabolism and atherosclerosis is not known. The purpose of this project is to answer the following questions: 1] Is plasma ASP elevated in metabolic states where plasma triglycerides and free fatty acids are raised? 2] Does ASP bind to a cell-surface protein in those cells where its activity is expressed? 3] What intracellular enzymes of lipid synthesis are effected by ASP? 4] Does ASP play an essential physiological role? 5] What are the structures of the functional domains of ASP? These questions will be answered by in vivo studies in hamsters, immunocytochemistry, subcellular organelle isolation, digital imaging microscopy, quantitative lipid analysis, gas and liquid chromatography, immunoassays, peptide sequencing and synthesis and structural analysis. The long term goal of this project is to identify the role of acylation stimulating proteins in controlling the flux of fatty acids in plasma and cells and to determine if an abnormality in the function of this class of proteins is important in abnormal triglyceride metabolism nd atherogenesis.

最近的证据表明，异常 甘油三酸酯和脂肪酸与过早的发生有关 冠状动脉疾病。 在细胞中，将脂肪酸用作 能量，作为膜生物发生的基础，作为前体 复杂的调节分子，例如类黄胶和血栓烷。 这 血浆中脂肪酸和许多细胞室之间的运输是 一个高度受监管的过程，使得变得更加复杂 餐后脂肪血症和随之而来的脂解。 一个主要主题 BCM-SCOR是甘油三酸酯和脂肪酸代谢异常 有助于动脉粥样硬化。 由于脂肪酸的升高可以 促进非常低密度脂蛋白的分泌增加 甘油三酸酯，脂肪酸和甘油三酸酯代谢直接 连接。 酰基化刺激蛋白（ASP或BP-1）是最近的三个 描述了促进脂肪内细胞内积累的蛋白质 酸及其随后的甘油三酸酯的转化，特别是在 周围组织。 该蛋白质在异常脂质中的作用 代谢和动脉粥样硬化尚不清楚。 这个项目的目的 是要回答以下问题：1]等离子体ASP升高 血浆甘油三酸酯和游离脂肪酸的代谢状态是 长大了？ 2]在那些细胞中，ASP与细胞表面蛋白结合 它的活动表达？ 3]哪种脂质的细胞内酶 合成是由ASP实现的？ 4] ASP可以发挥重要的生理学 角色？ 5] ASP功能域的结构是什么？ 这些 在仓鼠中的体内研究将回答问题， 免疫细胞化学，亚细胞器细胞器隔离，数字成像 显微镜，定量脂质分析，气体和液相色谱，， 免疫测定，肽测序，合成和结构分析。 该项目的长期目标是确定酰基化的作用 刺激蛋白质在控制血浆中脂肪酸的通量中 细胞并确定此类功能的异常 蛋白质在异常的甘油三酸酯代谢和动脉粥样硬化中很重要。