Effects of dietary saturated or polyunsaturated fat on hepatic glutathione S-transferase activity

Microsomal mixed function oxidases (MFO) responsible for phase I xenobiotic metabolism are partially dependent on dietary polyunsaturated fat. The reduced activity of the MFO when fat-free or saturated fat diets are fed has been associated with alterations of microsomal phospholipid fatty acid content. Glutathione S-transferases (GSH-transferases) catalyze phase II conjugation reactions, and are important detoxification pathways for highly reactive phase I-produced intermediates. We hypothesized that activity of membrane-bound, but not soluble, GSH-transferases would be affected by type of dietary fat. Rats were fed diets that contained either 20% coconut oil, 20% corn oil, or a mixture of 18% coconut oil plus 2% corn oil as the sole source of dietary fatty acids. At the end of the 3-week feeding period the activity of both microsomal and soluble fraction GSH-transferases of rat liver was determined. The original hypothesis that dietary fat type would alter membrane-bound transferase activity was not supported by the results since GSH-transferase activity in the microsomal fraction was not affected. However, feeding 20% coconut oil produced a 25 to 40% decrease in soluble transferase activity compared to corn oil feeding. The Michaelis constant (Km) for soluble GSH-transferase was threefold higher when the diet was devoid of polyunsaturated fat. Ultrafiltration of the soluble fraction to remove compounds with molecular weights below 50,000 did not eliminate the differences in transferase activity due to dietary fat. Separation of the soluble transferases by fast protein liquid chromatography indicated that quantities of the various transferases were affected equally by type of dietary fat. The results indicate that type of dietary fat may be important in determining the ability to detoxify carcinogens or other toxins that are conjugated with glutathione.