LIPID PHYSICAL CHEMISTRY IN BIOLOGY AND PATHOLOGY

生物学和病理学中的脂质物理化学

• 批准号: 2215991
• 负责人: DONALD M SMALL
• 金额: $ 219.39万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215991
• 关键词: blood lipoprotein; lipid disorder; lipid metabolism; lipid structure; membrane structure; molecular pathology

The overall objective is to apply physical-chemical rationale and techniques to the study of physiological and pathological processes involving lipids and specific proteins. Certain biological fluids (plasma, lymph, bile) contain lipids solubilized or suspended in aqueous systems frequently in association with specific proteins (e.g., lipoproteins). Disorders affecting lipid transport lead to the lipoproteinemias and often to a pathological distribution of lipids in tissues, cells, and fluids. Such disorders as atherosclerosis or gallstones may results. The plasma membranes of cells and/or intracellular organelles contain complex polar lipids which are not soluble but are structured in such a way as to combine fluidity with stability. Membrane composition varies from organelle to organelle and further, membranes are asymmetric with respect to both lipid and protein distribution. Membrane composition and symmetry can be altered by changes in the external environment or by internal metabolic perturbations and such changes may lead to defective function. Inherited deficiencies of enzymes involved in the catabolism of complex phospho- and sphingo-membranes, and lysosomes. These accumulations affect cell and organ function and give rise to the various familial lipidoses. Finally, certain less polar lipids (occurring for instance in adipose tissue, adrenal glands, gonads, liver and in the lesions of atherosclerosis) are organized in phases separated from the aqueous system. These phases may be liquid or more structure liquid crystalline or crystalline phases. The long term goals are to study the physical state and molecular interactions of lipids and proteins in living systems, to compare them to model systems, to learn how the physical state affects metabolism and vice versa, to understand the molecular basis and genetic control of lipoprotein secretion, interconversion, cell surface interaction and molecular exchange processes that occur in normal lipid transport, to understand the molecular basis of certain specific membrane functions and ultimately to understand the molecular basis of conditions in which lipids accumulate, such as atherosclerosis, the lipoproteinemias, and the lipidoses.

总体目标是应用物理化学原理， 研究生理和病理过程的技术 涉及脂质和特定蛋白质。 某些生物流体（血浆， 淋巴、胆汁）含有溶解或悬浮在含水系统中的脂质 通常与特定蛋白质（例如，脂蛋白）。 影响脂质转运的障碍导致脂蛋白血症， 脂质在组织、细胞和体液中的病理分布。 可能导致动脉粥样硬化或胆结石等疾病。 等离子体 细胞膜和/或细胞内细胞器含有复杂的极性 不可溶但以联合收割机 流动性与稳定性。 膜组成因细胞器而异， 细胞器和进一步，膜是不对称的两个脂质 蛋白质分布。 膜的组成和对称性可以被改变 通过外部环境的变化或内部代谢 扰动和这种变化可能导致功能缺陷。 继承 缺乏酶参与的催化剂的复杂磷酸和 鞘膜和溶酶体。 这些积累影响细胞， 器官功能，并引起各种家族性腹泻。 最后， 某些极性较小的脂质（例如存在于脂肪组织中， 肾上腺、性腺、肝脏和动脉粥样硬化病变）， 在与水体系分离的相中组织。 这些阶段可能是 液体或更高结构的液晶或结晶相。 的 长期目标是研究物理状态和分子相互作用 脂质和蛋白质在生命系统中的作用，将它们与模型系统进行比较， 了解身体状态如何影响新陈代谢，反之亦然， 了解脂蛋白的分子基础和遗传控制 分泌、相互转化、细胞表面相互作用和分子交换 过程中发生的正常脂质运输，了解分子 某些特定膜功能的基础，并最终了解 脂质积累条件的分子基础，如 动脉粥样硬化、脂蛋白血症和高剂量。