Consequences of erythrocytic glutathione reductase deficiency
Frischer, H.; Ahmad, T.
Journal of Laboratory and Clinical Medicine 109(5): 583-588
1987
ISSN/ISBN: 0022-2143 PMID: 3572207 Document Number: 289376
We have used 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) as a selective and irreversible inhibitor of oxidized glutathione reductase (GSSG-R) to determine how human erythrocytes with various degrees of GSSG-R deficiency recover their reduced glutathione (GSH) after exposure to acetylpheylhydrazine or diamide. Pentose phosphate dehydrogenases and glutathione synthesis were not inhibited, de novo glutathione synthesis was negligible within the experimental time frame, and the reappearance of GSH was strictly under the control of GSSG-R. Results obtained with acetylphenylhydrazine or diamide were concordant. In red cells stressed by these reagents, GSSG-R deficiency began to impair the regeneration of GSH only after > 80% of the normal enzyme activity had been abolished. Thereafter GSH recovery deteriorated as drug-induced GSSG-R depression increased. Only erythrocytes that had been rendered almost totally GSSG-R deficient, that is, had lost > 90% of baseline activity, became functionally equivalent to GdA- glucose-6-phosphate dehdyrogenase-deficient cells. The reserve capacity of GSSG-R in human erythrocytes is extremely large. Of all types of isolated GSSG-R "deficiencies" reported so far, only two can be considered pathogenically significant: the homozygous genetic defect found in a single family, and much more commonly, the acute pharmacologic phenocopy induced by BCNU. (J Lab Clin Med 1987;109:583-8).