METABOLIC AND STRUCTURAL STUDIES OF POLYUNSATURATED LIPIDS IN CELL MEMBRANES

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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.