NMR STUDIES OF WEAKLY POLAR LIPIDS

胆固醇酯（CE）、二酰基甘油（DAG）和三酰基甘油（TAG） 是正常和异常人体生理学中的重要脂质。 CE是 胆固醇转运和代谢的中间体， 动脉粥样硬化斑块的组成部分; 1，2 DAG是动脉粥样硬化斑块中的“第二信使”。 许多细胞信号转导过程;和TAG是主要的存储 身体脂肪的形式。 这些不溶于水的中性分子， 形成分离相，也在有限程度上分配到磷脂中 层状结构，因为它们的弱极性。 一个现行假设 这一建议的一个重要方面是，位于界面的弱极性脂质相互作用 与酶、转运蛋白和膜蛋白结合， 界面性质，如溶解度、构象和 流动性是这些互动的关键决定因素。 总的目标是 阐明解释脂质运输和代谢的物理性质 为人类疾病的诊断和治疗提供了新的方法 疾病 这些脂质的界面性质将通过高密度聚乙烯来探测。 分辨率，魔角旋转（MAS）和固态NMR方法， 13 C、1H和31 P核，结合其他适当的物理 技术. 这些研究将检查天然的生物脂质（ 13 C-羰基富集在某些情况下）和广泛使用的，非- 可代谢的CE类似物，胆固醇油基醚。 MAS和固态 NMR方法将检查弱极性脂质的界面性质， 模拟膜或磷脂单层的多层系统 低曲率的表面，高分辨率的方法将检查一个 高度弯曲表面的模型系统（小单层囊泡）。 一 一种基于13 C化学位移的新方法，将测试什么样的相互作用 性质影响CE和TAG通过载体蛋白的转运。 的 中链TAG与CE和长乳胶粒的竞争 适用于TAG代谢受损患者的胃肠外喂养。 CE的体积性质在动脉粥样硬化形成中是重要的，并且结构性质在动脉粥样硬化形成中是重要的。 动脉粥样硬化病变中CE和其他脂质的组织和动力学 将通过高分辨率和MAS NMR检查胆固醇喂养的兔的。 核磁共振数据将仔细与化学，微观和 相同样品的量热数据。 这些研究是必不可少的 未来高分辨率和成像核磁共振研究的先驱。

Cholesteryl esters (CE), diacylglycerols (DAG) and triacylglycerols (TAG) are important lipids in both normal and abnormal human physiology. CE are intermediates in cholesterol transport and metabolism and a major chemical component of atherosclerotic plaques; 1,2 DAG are 'second messengers' in many cellular signal transduction processes; and TAG are the main storage form of body fats. These water-insoluble, neutral molecules, which readily form separate phases, also partition to limited extents into phospholipid lamellar structures because of their weak polarity. A working hypothesis of this proposal is that interfacially-located weakly polar lipids interact with enzymes, transport proteins and membrane proteins, and that interfacial properties such as extent of solubility, conformation and mobility are key determinants of these interactions. A general goal is to elucidate physical properties that explain lipid transport and metabolism and that will provide new diagnostic and treatment methods for human disease. Interfacial properties of these lipids will be probed by high resolution, magic angle spinning (MAS), and solid state NMR methods for 13C, 1H and 31P nuclei, in conjunction with other appropriate physical techniques. These studies will examine native, biological lipids (with 13C-carbonyl enrichment in some cases) and the widely used, non- metabolizable CE analogue, cholesterol oleyl ether. MAS and solid state NMR methods will examine interfacial properties of weakly polar lipids in multilamellar systems which model membranes or phospholipid monolayer surfaces with low curvature, and high resolution methods will examine a model system for highly curved surfaces (small unilamellar vesicles). A new methodology, based on 13C chemical shifts, will test what interaction properties influence transport of CE and TAG by carrier proteins. The competition of medium chain TAG with CE and long emulsion particles suitable for parenteral feeding to patients with impaired TAG metabolism. Bulk properties of CE are important in atherogenesis, and the structural organization and dynamics of CE and other lipids in atherosclerotic lesions of cholesterol-fed rabbits will be examined by high resolution and MAS NMR. NMR data will be carefully correlated with chemical, microscopic and calorimetric data on the same sample. Such studies are essential precursors to future high resolution and imaging NMR studies on humans.