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: 3813487
• 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/3813487
• 关键词: arachidonate; brain metabolism; chemical structure function; dietary supplements; enzyme inhibitors; erythrocyte membrane; ethanol; fatty acid metabolism; high performance liquid chromatography; human tissue; lipid metabolism; lipid structure; lipoxygenase; mass spectrometry; membrane lipids; membrane structure; muscle contraction; nutrition related tag; omega 3 fatty acid; phospholipids; platelets; unsaturated fatty acids

The principal objective of this study is to elucidate the structural and metabolic functions of polyunsaturated fatty acids and 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, docosaheaenoate (C22:6w3) and, to a lesser extent, on arachidonate (C20:4w6). Progress has been made in the development of a covalent labelling technique that allows the study of aminophospholipid molecular species composition and membrane topology. Data for reference purposes has been obtained for more than 50 species in the human erythrocyte. Generally, the phenomenon of molecular species asymmetry has been confirmed, i.e. polyunsaturates are selectively localized on the cytoplasmic leaflet of the plasma membrane. Dietary supplementtation with w-3 fatty acids leads to replacement primarily of alkenyl-20:4w6 phosphatidylethanolamines (PE) with the corresponding 20:5w3 or 22:6w3 and decreased 18:2w6 and 20:4w6 products relative to an w-6 supplemented group. Urinary PGI3 metabolites are also increased but there was no evidence of a decrease in PGI2 metabolism. Hydroxy-docosahexaenoates (HDHE) have been biosynthesized for pharmacological experiments in which it was observed that they have a weak contractile action on smooth muscle and can also antagonize thromboxane- induced contractility. Platelet HDHEs were steroselectively formed but the brain p0roducts appear to be racemic mixtures.

本研究的主要目的是阐明结构和