Effects of Omega-3 Polyunsaturated Fatty Acids on Human Leukocyte Function and Biochemistry

Abstract

The 5-lipoxygenase pathway, which generates monohydroxy-fatty acids and leuko-trines via metabolism of arachidonic acid, is distinguished in a number of ways from the better-known cyclooxygenase pathway, which produces prostaglandins, thromboxanes, and heptadecatrienoic acid. The 5-lipoxygenase pathway has been identified in a limited number of cell types, the majority of which are of bone marrow origin; its expression requires activation of the initial enzyme in the cascade (the 5-lipoxygenase enzyme) as well as substrate availiability (Borgeat and Samuelsson 1979) for synthesis of products. In contrast, the cyclooxygenase pathway is virtually ubiquitous among nucleated cells, merely requiring substrate availability for product generation. Arachidonic acid (AA, 20:4) is the major substrate for both pathways, and is an ω-6 polyunsaturated fatty acid (i.e., the terminal unsaturation is six carbons from the ω-methyl group); it is derived from ω-6 polyunsaturated fatty acids of land-based plants and animals. Eicosapentaenoic acid (EPA; 20:5, ω-3) and docosahexaenoic acid (DHA; 22:6, ω-3) are both prominent in marine organisms and especially as esterified components of fish oil triglycerides. Both EPA and DHA inhibit the cyclooxygenase in a cell-free preparation and EPA has been shown to inhibit this enzyme in intact cells (Needleman et al. 1979; Corey et al. 1983). The effects of the ω-3 polyunsaturated fatty acids on the 5-lipoxygenase pathway in human cells both from healthy volunteers and patients with defined disease states are being studied.