METABOLIC AND STRUCTURAL STUDIES OF POLYUNSATURATED LIPIDS IN CELL MEMBRANES

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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.