POLYUNSATURATED PHOSPHOLIPIDS IN MEMBRANE FUNCTION

我们长期以来对膜磷酸甘油酯很感兴趣 含有具有 4 至 6 个顺式双键的酯化脂肪酸。 这些脂肪酸是多不饱和脂肪酸家族的成员 灵长类动物或其他脊椎动物无法从头形成的酸， 如果这些动物要繁殖，就必须在饮食中提供， 发展、成长并保持健康。 脂肪酸还包括 兴趣，因为它们会受到人为氧化和 防止这种氧化并修复其影响的特殊机制， 并且有理由相信这些机制的失调 发生在老年人、动脉粥样硬化和 神经退行性疾病，如阿尔茨海默病、帕金森病 疾病和肌萎缩侧索硬化症。 我们一直在探索 含有多不饱和的磷酸甘油酯的可能性 具有四个或更多顺式双键的脂肪酸通常具有 对神经质膜脂具有重要的结构作用 双层。 我们正在完成详细的分子 建模研究以确定可能影响能力的因素 磷酸甘油酯在模拟中相互作用 单层。 我们几乎完成了一项实验研究 将这些磷酸甘油酯包装在单层中。 实验与 含有磷酸甘油酯的单层囊泡正在进行中， 以及猕猴大脑前额皮质突触体的实验 质膜和突触小泡（见上文）已规划。 资助 NIH 拨款 RR00166 和霍华德休斯医学研究所。 [该项目也在神经科学核心部分进行了报道。]

We have had a long-standing interest in membrane phosphoglycerides that contain esterified fatty acids with 4 to 6 cis double bonds. These fatty acids are members of families of polyunsaturated fatty acids that cannot be formed de novo by primates or other vertebrates, and must be provided in the diet if these animals are to reproduce, develop, grow, and maintain their health. The fatty acids also are of interest because they are subject to artifactual oxidation and to special mechanisms to prevent this oxidation and repair its effects, and there is reason to believe that disorders of these mechanisms occur in aged individuals, in atherosclerosis, and in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We have been exploring the possibility that phosphoglycerides that contain polyunsaturated fatty acids with four or more cis double bonds may normally have an important structural effect on the nerve plasm a membrane lipid bilayer. We are in the process of completing detailed molecular modeling studies to identify factors that might influence the ability of the phosphoglycerides to interact with each other in simulated monolayers. We have almost completed an experimental study of the packing of these phosphoglycerides in monolayers. Experiments with unilamellar vesicles containing the phosphoglycerides are underway, and experiments with macaque brain prefrontal cortex synaptosome plasma membranes and synaptic vesicles (see above) are planned. FUNDING NIH grant RR00166 and the Howard Hughes Medical Institute. [This project was also reported in the Neuroscience Core section.]