Tissue Glutathione as a Cyst(e)ine Reservoir during Cystine Depletion in Growing Rats

Abstract

Previous data suggest that liver glutathione (GSH) serves as a cyst(e)ine reservoir in rats starved or fed cyst(e)ine-deficient diets. In the present study we investigated whether extrahepatic tissue GSH concentrations also decreased during cystine (Cys-Cys) depletion and whether excess dietary cystine increased tissue GSH and cysteine (Cys) concentrations. Five groups of growing rats (80–100 g) were fed diets containing crystalline L-amino acids differing in methionine (Met) and cystine (Cys-Cys) content for 15 days. All diets were isonitrogenous (1.3 g/100 g diet) and provided the minimum Met (0.17%) required by growing rats. Diet 1 provided 0.17% Met and 0% Cys-Cys, diet 2 (the recommended diet) provided 0.17% Met and 0.26% Cys-Cys, diet 3 provided 0.50% Met and 0% Cys-Cys, diet 4 provided 0.17% Met and 0.39% Cys-Cys and diet 5 provided 0.17% Met and 0.52% Cys-Cys. Diets 2 and 3 were isosulfurous at 3.3 mmol/100 g diet. Diets 4 and 5 provided 50 and 100%, respectively, more Cys-Cys than required when 0.17% Met was present. Animals fed diet 1 (Cys-Cys depletion) had significantly decreased (P < 0.05) liver, muscle, spleen, heart and thymus GSH concentrations, whereas brain, small intestine and erythrocyte GSH concentrations remained unchanged. Although brain and small intestine Cys concentrations were not affected by Cys-Cys depletion, spleen, heart and liver Cys concentrations decreased significantly (P < 0.05). Feeding Cys-Cys above the requirement level did not increase GSH and Cys concentrations of any tissue except liver where Cys levels were elevated. The data indicate that liver, muscle, spleen, heart and thymus GSH serve as Cys reservoirs during Cys-Cys depletion.