Eicosanoid Metabolism and Biological Effects of n6 and n3 Fatty Acids

When humans ingest fish or fish oil, the ingested EPA and DHA partially replace the n-6 fatty acids (especially AA) in cell membranes, particularly those of platelets, erythrocytes, neutrophils, monocytes, and liver cells.

Because of the increased amounts of n-6 fatty acids in the Western diet, the eicosanoid metabolic products from AA, specifically prostaglandins, thromboxanes, leukotrienes, hydroxy fatty acids, and lipoxins, are formed in larger quantities than those formed from n-3 fatty acids, specifically EPA. As a result (Figure 5), ingestion of EPA and DHA from fish or fish oil leads to: (1) decreased production of prostaglandin E2 metabolites; (2) decreased concentrations of thromboxane A2, a potent platelet aggregator and vasoconstrictor; (3) decreased formation of leukotriene B4, an inducer of inflammation and a powerful inducer of leukocyte chemotaxis and adherence; (4) increased concentrations of thromboxane A3, a weak platelet aggregator and vasoconstrictor; (5) increased concentrations of prostacyclin prostaglandin I3 (PGI3), leading to an overall increase in total prostacyclin by increasing PGI3 without decreasing PGI2 (both PGI2 and PGI3 are active vasodilators and inhibitors of platelet aggregation); and (6) increased concentrations of leukotriene B5, a weak inducer of inflammation and a chemotactic agent. The eicosanoids from AA are biologically active in small quantities and if they are formed in large amounts, they contribute to the formation of thrombi and atheromas; the development of allergic and inflammatory disorders, particularly in susceptible people; and cell proliferation. Thus, a diet rich in n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggre-gatory, with increases in blood viscosity, vasos-pasm, and vasoconstriction and decreases in bleeding time. Bleeding time is shorter in groups of patients with hypercholesterolemia, hyperlipo-proteinemia, myocardial infarction, other forms of atherosclerotic disease, type 2 diabetes, obesity, and hypertriglyceridemia. Atherosclerosis is a major complication in type 2 diabetes patients. Bleeding time is longer in women than in men and in younger than in older persons. There are ethnic differences in bleeding time that appear to be related to diet. The hypolipidemic, antithrom-botic, anti-inflammatory, and anti-arrhythmic effects of n-3 fatty acids have been studied extensively in animal models, tissue cultures, and cells (Table 7).

Diet

C18:2n-6 linoleic acid (LA)

C18:3n-6 gamma linolenic acid (GLA)

C20:3n-6 dihomogamma linolenic acid delta6-desaturase elongase

delta5-desaturase

C18:3n-3 alpha linolenic acid (ALA)

C18:4n-3 C20:4n-3

C20:5n-3 eicosapentaenoic acid (EPA)

C20:5n-3 eicosapentaenoic acid (EPA)

C22:5n-6 docosapentaenoic acid

Figure 2 Essential fatty acid metabolism: desaturation and elongation of n-6 and n-3.

C24:5n-6

C22:5n-6 docosapentaenoic acid

Figure 2 Essential fatty acid metabolism: desaturation and elongation of n-6 and n-3.

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