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: 3817395
• 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/3817395
• 关键词: arachidonate; brain metabolism; cerebral ischemia /hypoxia; chemical structure function; enzyme inhibitors; erythrocyte membrane; ethanol; fatty acid metabolism; high performance liquid chromatography; human tissue; laboratory rat; leukotrienes; lipid metabolism; lipid structure; lipoxygenase; mass spectrometry; membrane lipids; membrane structure; muscle contraction; omega 3 fatty acid; phospholipids; platelets; thromboxanes; unsaturated fatty acids

The principal objective of 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. Human platelets produce ll(S), 14(S)- and 17(S)-hydroxy-22:6w3 when the free fatty acid is added to a cell suspension. This reaction is blocked by lipoxygenase inhibitors but stimulated by alcohol. Similar products are also generated in the nervous system in vivo and this metabolite formation is blocked by lipoxygenase inhibitors but stimulated by cerebral ischemia. The 14(S)-hydroxy-22:6w3 is a fairly potent contractile agent on smooth muscle preparations and can antagonize the contractile action of a thromboxane agonist. Alcohol inhalation decreases the level of platelet 20:4w6 unless a source of dietary 18:3w6 is present. A sensitive method for aminophospholipid molecular species analysis has been developed to follow these leads in terms of both compositional and topographic analyses in alcoholics.

本研究的主要目的是阐明 多不饱和脂肪酸的结构和代谢功能 或磷脂，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 研究集中在大脑的主要多核细胞上， 二十二碳六烯酸（C22：6 w3），在较小程度上，花生四烯酸 (C20：4w6）。 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 人血小板产生11（S）、14（S）-和 17（S）-羟基-22：6 w3，当将游离脂肪酸加入细胞时 悬浮液 这一反应被脂氧合酶抑制剂阻断 但受酒精刺激。 类似产品也产生于 体内的神经系统和这种代谢物的形成被阻断 由脂氧合酶抑制剂，但刺激脑缺血。 14（S）-羟基-22：6 w3是一种相当有效的收缩剂， 平滑肌制剂，并能拮抗收缩 血栓素激动剂的作用。 酒精吸入会降低血小板20：4 w 6水平，除非 存在膳食18：3 W 6的来源。 一种灵敏的方法， 氨基磷脂分子种类分析已经发展到 在构图和地形上都遵循这些线索 分析酗酒者。