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

Publisher Website
Google Scholar
Abstract
The significance of glutathione S-conjugate in the regulation of glutathione synthesis was studied using human erythrocyte .gamma.-glutamylcysteine synthetase [EC 6.3.2.2]. 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 .gamma.-glutamylcysteine synthetase activity was obtained at .apprx. 1 .mu.M; 50 .mu.M glutathione S-conjugate in the presence of 10 mM glutathione actually increased the enzyme activity 2-fold 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 [EC 2.5.1.18], the level of glutathione synthesis increased. Glutathione S-conjugate probably plays a role in stimulating the synthesis of glutathione.