Significance of glutathione S-conjugate for glutathione metabolism in human erythrocytes.
The significance of glutathione S-conjugate in the regulation of glutathione synthesis was studied using human erythrocyte gamma-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 gamma-glutamylcysteine synthetase activity was obtained at approximately 1 microM; 50 microM 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.
D002384:Catalysis; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000097:blood*; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010453:Peptide Synthases / Q000097:blood*
C030190:S-(2,4-dinitrophenyl)glutathione; D005982:Glutathione Transferase; D010453:Peptide Synthases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione