NMR STUDIES OF WEAKLY POLAR LIPIDS

胆固醇酯(CE)、二酰基甘油(DAG)和三酰基甘油(TAG) 在正常和异常的人体生理中都是重要的脂类。行政长官是 胆固醇运输和代谢的中间体和一种主要化学物质 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；和标签是主要的存储 身体脂肪的形式。这些不溶于水的中性分子，很容易 形成单独的相，也在有限的范围内分割成磷脂 片状结构，因为它们的弱极性。一个可行的假说 这一提议的关键是，位于界面位置的弱极性脂类相互作用 与酶、运输蛋白和膜蛋白结合， 界面性质，如溶解度、构象和 机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新陈代谢的物理性质 这将为人类提供新的诊断和治疗方法 疾病。这些脂类的界面性质将通过高密度脂蛋白来探测 分辨率、魔角旋转(MAS)和固体核磁共振方法 13C、1H和31P核，以及其他适当的物理 技巧。这些研究将检查天然的生物脂质(与 在某些情况下，13C-羰基浓缩)和广泛使用的、非 可代谢的CE类似物，胆固醇油醚。MAS和固态 核磁共振方法将研究弱极性脂类在 模拟膜或磷脂单分子层的多层体系 具有低曲率和高分辨率方法的曲面将检查 高度弯曲表面(小单层囊泡)的模型系统。一个 基于13C化学位移的新方法将测试什么相互作用 载体蛋白的性质影响CE和Tag的转运。这个 中链标签与CE和长乳胶颗粒的竞争 适用于TAG代谢受损患者的肠外喂养。 CE的整体性质在动脉粥样硬化形成中很重要，而CE的结构 CE等脂类在动脉粥样硬化病变中的组织和动态 将用高分辨率和MAS核磁共振检查高胆固醇喂养的兔。 核磁共振数据将与化学、显微和 同一样品上的量热数据。这样的研究是必不可少的 未来对人体进行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.