METABOLIC AND STRUCTURAL STUDIES OF POLYUNSATURATED LIPIDS IN CELL MEMBRANES

本研究的主要目的是阐明结构和 多不饱和脂肪酸和磷脂的代谢功能， 特别是通过乙醇对其进行调节。的几项解决方案 这个问题，包括细胞脂质组成的研究， 膜不对称、脂肪酸氧化和膳食补充。在 特别是，这些研究集中在大脑的主要多功能性， 二十二碳六烯酸（C22：6 w3），在较小程度上，花生四烯酸 (C20：4w6）。 共价标记技术的发展已取得进展 这使得研究氨基磷脂分子种类组成成为可能 和膜拓扑学。已获得以下数据供参考： 人体红细胞中有50多种。一般来说， 分子物种不对称性已得到证实，即多不饱和化合物是 选择性地定位在质膜的细胞质小叶上。 饮食中添加w-3脂肪酸会导致替代 主要是烯基-20：4 w 6磷脂酰乙醇胺（PE）， 相应的20：5 w3或22：6 w3和减少的18：2 w 6和20：4 w 6产品 相对于W-6补充组。尿PGI 3代谢物也是 增加，但没有证据表明PGI 2代谢减少。 羟基-二十二碳六烯酸（HDHE）已被生物合成， 药理学实验，其中观察到它们具有弱的 对平滑肌的收缩作用，也可以拮抗血栓素- 诱导收缩力。血小板HDHE是立体选择性形成的， 脑产物似乎是外消旋混合物。

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.