BIOLOGICAL FUNCTIONS OF ESSENTIAL FATTY ACIDS

这项研究的目的是研究 视网膜必需脂肪酸缺乏的基础，这是视网膜必需脂肪酸缺乏的一部分 它包含了一个有价值的、独一无二的模型， 哺乳动物的神经系统 目前的知识表明， 从必需ω 3脂肪酸衍生的链状多不饱和脂肪酸 酸可能在视网膜和大脑发育中起重要作用。 对大鼠和恒河猴的研究表明， 由于饮食改变引起的眼睛的电反应功能 含有二十二碳六烯酸的膜磷脂含量 (22：6 Ω 3，缩写为DHA）。 这些研究激发了讨论 关于长链多不饱和脂肪酸 如DHA应该添加到婴儿配方奶粉中。 此外， 对omega 3/omega 6必需脂肪酸比例的关注增加 西方饮食中的酸。 视网膜杆中的视觉过程是 由视紫红质的构象变化引发 包埋在杆外节（ROS）的膜内。 我们将 检验视网膜杆盘膜的特性 脂质和蛋白质成分通过它们的 对视紫红质MI-MII构象转变的影响， 视觉刺激的触发事件 视网膜ROS盘膜 磷脂含量非常丰富， 多不饱和脂肪酸，包括DHA和花生四烯酸 (20：4 Ω 6）。 我们认为视紫红质与 多不饱和膜脂质调节MI的自由能， MII构象状态，从而改变关键扩增步骤 涉及信号转导G蛋白（transducin）和cGMP 磷酸二酯酶 这些反过来又影响cGMP门控血浆的关闭， 膜钠离子通道，随后产生一个视觉 神经冲动。 多不饱和膜脂含量的变化 由于饮食或疾病的变化， 视紫红质，并影响视网膜的电反应。 Flash 将应用并进一步开发光解方法， 多不饱和脂质对大鼠肝细胞MI-MII转变的影响 膜重组体中的视紫红质。 将特别强调 在研究多不饱和酰基链 组成以及膜的极性头基组成 磷脂 多不饱和膜磷脂的影响 在视觉光反应的后期放大阶段， 研究包括G蛋白的结合和激活 （transducin）转化为光解的视紫红质，随后激活cGMP 磷酸二酯酶 最后，核磁共振（NMR） 光谱学将产生物理化学的补充知识 多不饱和磷脂的性质及其与 膜中的视觉蛋白。 全面了解联合国系统的作用 多不饱和磷脂在视觉过程中将提供 与必需欧米伽3膳食调查结果的关系 动物和人类的脂肪酸缺乏症。

The objective of the proposed research is to investigate the molecular basis for essential fatty acid deficiency in the retina, which is part of the brain and comprises a valuable and uniquely accessible model for the mammalian nervous system. Current knowledge indicates that long chain polyunsaturated fatty acids derived from essential omega3 fatty acids may play an important role in retinal and brain development. Studies of both rats and rhesus monkeys indicate a marked alteration of the electrical response functions of the eye due to dietary alteration of the content of membrane phospholipids containing docosahexaenoic acid (22:6omega3, abbreviated DHA). These studies have stimulated discussion regarding the question of whether long-chain polyunsaturated fatty acids such as DHA should be added to infant formulas. Moreover there is increased concern regarding the ratios of omega3 / omega6 essential fatty acids in the western diet. The process of vision in retinal rods is triggered by a conformational change of the visual protein rhodopsin embedded within the membranes of the rod outer segment (ROS). We will test the hypothesis that the properties of the retinal rod disk membrane lipid and protein constituents govern visual function through their influences on the MI-MII conformational transition of rhodopsin, the triggering event in visual excitation. The retinal ROS disk membranes are extraordinarily abundant in phospholipids, containing highly polyunsaturated fatty acidS, including DHA and arachidonic acid (20:4omega6). We propose that interactions of rhodopsin with polyunsaturated membrane lipids modulate the free energies of the MI and MII conformational states, thus altering key amplification steps involving the signal transducing G protein (transducin) and cGMP phosphodiesterase. These in turn affect closure of the cGMP-gated plasma membrane sodium channels, and subsequently the generation of a visual nerve impulse. Changes in the content of polyunsaturated membrane lipids due to diet or disease shifts the MI-MII equilibrium of photolyzed rhodopsin, and influence the electrical response of the retina. Flash photolysis methods will be applied and further developed to monitor the influences of polyunsaturated lipids on the MI-MII transition of rhodopsin in membrane recombinants. Particular emphasis will be placed upon investigating the role of both the polyunsaturated acyl chain composition as well as the polar head group composition of the membrane phospholipids. The influences of polyunsaturated membrane phospholipids on later amplification stages of the visual photoresponse will be investigated including the binding and activation of the G protein (transducin) to photolyzed rhodopsin, and subsequent activation of cGMP phosphodiesterase. Finally, nuclear magnetic resonance (NMR) spectroscopy will yield complementary knowledge of the physicochemical properties of polyunsaturated phospholipids and their interactions with visual proteins in membranes. A comprehensive picture of the role of polyunsaturated phospholipids in the visual process will be provided in relation to the results of dietary investigations of essential omega3 fatty acid deficiency in animals and humans.