METABOLIC AND STRUCTURAL STUDIES OF POLYUNSATURATED LIPIDS IN CELL MEMBRANES

细胞膜中多不饱和脂质的代谢和结构研究

• 批准号: 3821237
• 负责人: N SALEM
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821237
• 关键词: aorta; arachidonate; brain metabolism; chemical structure function; erythrocyte membrane; ethanol; fatty acid metabolism; high performance liquid chromatography; human tissue; leukotrienes; lipid metabolism; lipid structure; lipoxygenase; mass spectrometry; membrane lipids; membrane structure; muscle contraction; omega 3 fatty acid; phospholipids; unsaturated fatty acids

The principal objective os this study is to elucidate the structural and metabolic functions of polyunsaturated fatty acids or phospholipids with particular reference to their modulation by ethanol. Several approaches to this problem were taken including studies of cellular lipid composition, membrane asymmetry, fatty acid oxygenation and dietary supplementation. In particular, these studies focused on the major polyunsaturate of brain, docosahexaenoate (C22:6w3) and, to a lesser extent, on arachidonate (C20:4w6). The characterization of the enzymatic oxygenation of docosahexaenoate (22:6w3) was further characterized as a lipoxygenase system. Rat brain homogenate enzyme was sensitive to the lipoxygenase inhibitors ETYA, NDGA and caffeic acid but insensitive to cyclooxygenase inhibitors such as indomethacin. Preliminary results indicate that monohydroxylated-22:6 derivatives are formed by rat brain in vivo. This is the first demonstration of a 22:6 lipoxygenase product formed in vivo in any mammalian organism and is therefore of general significance. A second avenue of investigation of the biological effects of polyunsaturates involved the effects of the 22:6 fatty acid on aortic contractility. It was observed that micromolar concentrations of 22:6 produced a decrease in muscle tone in the rat aorta and that this effect does not appear to be mediated by prostaglandins or leukotriene formation. Continued development of thermospray liquid chromatographic/mass spectrometric (LC/MS) techniques for the analysis of phospholipid species has made possible a rapid, detailed and efficient analysis of all of the major lipid classes. Progress has been made in the development of quantitative methods and initial results and ethanol exposure on biological tissue lipid composition is presented.

本研究的主要目的是阐明 和多不饱和脂肪酸的代谢功能， 磷脂，特别涉及它们的调节， 乙醇 针对这一问题采取了若干办法，包括 细胞脂质组成、膜不对称性、脂肪 酸氧化和膳食补充。 特别是， 这些研究集中在脑的主要多核性， 二十二碳六烯酸（C22：6 w3），在较小程度上， 花生四烯酸（C20：4 w 6）。 的酶促氧化的表征 二十二碳六烯酸酯（22：6 w3）进一步表征为 脂氧合酶系统 大鼠脑组织匀浆酶敏感 脂氧合酶抑制剂ETYA、NDGA和咖啡酸， 对环加氧酶抑制剂如吲哚美辛不敏感。 初步结果表明，单羟基-22：6 衍生物由大鼠脑在体内形成。 这是第一 证明了在体内形成的22：6脂氧合酶产物， 任何哺乳动物有机体，因此具有普遍意义。 第二种研究生物效应的途径是： 多不饱和脂肪酸涉及22：6脂肪酸对 主动脉收缩力 据观察，微摩尔 22：6的浓度产生了肌肉张力的下降， 大鼠主动脉，这种作用似乎不是由 白藜芦醇或白三烯形成。 热喷涂液的持续发展 色谱/质谱（LC/MS）技术， 磷脂种类的分析使得快速， 对所有主要脂质类别进行详细有效的分析。 定量开发取得进展 方法和初步结果以及乙醇暴露对生物 组织脂质组成。