Significance of glutathione S‐conjugate for glutathione metabolism in human erythrocytes

Abstract

The significance of glutathione S‐conjugate in the regulation of glutathione synthesis was studied using human erythrocyte γ‐glutamylcysteine synthetase. Feedback inhibition of the enzyme by reduced glutathione was released by the addition of the glutathione S‐conjugate (S‐2,4‐dinitrophenyl glutathione). A half‐maximal effect of glutathione S‐conjugate on γ‐glutamylcysteine synthetase activity was obtained at approximately 1 μM; 50 μM glutathione S‐conjugate in the presence of 10 mM glutathione actually increased the enzyme activity twofold above uninhibited levels. Glutathione S‐conjugate had no effect on the enzyme activity in the absence of glutathione. When erythrocytes were exposed to the electrophile 1‐chloro‐2,4‐dinitrobenzene, which forms a glutathione S‐conjugate by the catalytic reaction of glutathione S‐transferase, the level of glutathione synthesis increased. These data suggest that glutathione S‐conjugate plays a role in stimulating the synthesis of glutathione. Copyright © 1984, Wiley Blackwell. All rights reserved