The effect of dietary fats on the composition of the liver endoplasmic reticulum and oxidative drug metabolism

Abstract

1. The dependence of the rate of oxidative demethylation in the liver endoplasmic reticulum on the fatty acid composition of the endoplasmic reticulum has been studied by varying the lipid content of the diet.2. The rate of oxidative demethylation was markedly dependent on the percentage of linoleic acid (18:2) incorporated into the membrane. Feeding diets containing (g/kg) 100 coconut oil, 100 lard or 100 maize oil caused respectively the incorporation of 7.6, 10.3 and 25.1% linoleic acid (18:2) and a demethylation rate of 3.26, 3.15 and 5.03 nmol formaldehyde/min per mg protein. Feeding 100 g herring oil/kg diet caused incorporation of only 5.1% C18:2but also 27.2% ωw3 unsaturated fatty acids, including 8.7% eicosapentaenoic acid (20:5) and 17.0% docosahexaenoic acid (22.6) and caused a very high rate of oxidative demethylation (6.53 nmol formaldehyde/min per mg protein).3. Destruction of the polyunsaturated fatty acids in herring oil by irradiation with 400 krad caused incorporation of a smaller quantity of ωw3 unsaturated acids into the endoplasmic reticulum and decreased the rate of oxidative demethylation (4.83 nmol formaldehyde/min per mg protein).4. The inductive effects of phenobarbitone on oxidative demethylation were partially dependent on changes in the fatty acid composition of the endoplasmic reticulum. Phenobarbitone (100 mg/kg) increased the percentage of C18:2from 25.1 to 29.4% in rats given a maize-oil diet, increased the percentage of C20:5from 8.7 to 10.3% in rats given a herring-oil diet and decreased the percentage of arachidonic acid (20:4) and C22:6in rats given a lard, maize-oil, herring-oil or irradiated-herring-oil diet.5. Intraperitoneal α-tocopherol (50 mg/kg) increased the percentage of C20:4from 11.1 to 13.1% in rats given a lard diet and from 5.9 to 7.3% in rats given a herring-oil diet.6. It is concluded that dietary C18:2is an important factor in the regulation of the rate of oxidative demethylation in the liver endoplasmic reticulum but this may be replaced effectively by dietary C20:5ω3 and C22:6ω3 acids. Oxidative demethylation is regulated by changes in the fatty acid composition of the membranes of the liver endoplasmic reticulum.