Variations in Dietary Protein but Not in Dietary Fat Plus Cellulose or Carbohydrate Levels Affect Cysteine Metabolism in Rat Isolated Hepatocytes

To determine if previously observed effects of dietary protein on hepatic cysteine metabolism were due specifically to increases in dietary protein or to the accompanying decreases in dietary carbohydrate, two experiments were conducted. In one experiment, rats were fed diets that contained different levels of protein vs. an isocaloric mixture of fat + cellulose and a constant amount of carbohydrate. In the other, rats were fed diets that contained a constant amount of protein but different levels of carbohydrate vs. an isocaloric mixture of fat + cellulose. Diets were fed for 2-3 wk and hepatocytes were then isolated. Hepatic cysteine dioxygenase activity increased and cysteinesulfinate decarboxylase and γ-glutamylcysteine synthetase activities decreased in a stepwise manner when protein was added to the diet at the expense of fat + cellulose. Changes in cysteine dioxygenase, cysteinesulfinate decarboxylase and γ-glutamylcysteine synthetase activities were consistent with changes in rates of cysteine catabolism, taurine production and glutathione synthesis, respectively, by intact hepatocytes incubated with 0.2 mmol/L cysteine. When the carbohydrate to fat + cellulose ratio was varied, but the protein level was held constant, little or no change in enzyme activities or levels of metabolite production was observed. Regulation of the activities of enzymes involved in cysteine metabolism is predominantly due to changes in dietary protein intake and not to the associated changes in intake of other dietary macronutrients.