Disulphide reduction in glutathione-deficient erythrocytes from a patient with pyroglutamic acidemia

Erythrocytes from a patient with pyroglutamic acidemia, containing about 5% of the normal content of glutathione, were able to reduce cystamine at a relatively high rate (about 50% that of normal cells) at low concentrations of the disulphide. Compared to normal cells, the reduction of disulphide by the patient's cells were highly sensitive to inhibition by high concentrations of the disulphide. This inhibition was noted whether glucose or inosine were used as carbohydrate substrate, and was also present when hemolysates were used and NADPH was added directly to the reaction mixture. The "disulphide poisoning" is assumed to be due to the formation of mixed disulphides at the expense of oxidized glutathione available for reduction by glutathione reductase. The glutathione/glutathione reductase system is probably the only disulphide reducing system of importance in human erythrocytes.