Enhanced Binding of FAD to Glutathione Reductase in G6PD Deficiency

Abstract

THE activity of glutathione reductase (GR) in erythrocytes deficient in glucose-6-phosphate dehydrogenase (G6PD) is approximately 1.5 to 2 times higher than in red cells with normal G6PD activity¹. This may provide a compensatory mechanism for the defect in glutathione reduction in G6PD deficient cells. The cause of the increased activity of GR in G6PD deficiency is unknown and the possibility of increased production of GR in erythrocyte precursors of G6PD deficient individuals seems unlikely. The lower mean red cell age, resulting from a moderately shortened life span of G6PD deficient erythrocytes², may play a part but is unlikely to account entirely for the marked increase in GR activity. Recently Beutler³ reported a stimulation of erythrocyte GR in normal subjects by flavin–adenine dinucleotide (FAD) in vitro and by supplementation of its precursor riboflavin in vivo. GR activity was shown to depend on dietary intake of riboflavin, but even in persons with a relatively high intake of this vitamin GR does not seem to be saturated with FAD⁴. These findings suggest that differences of FAD binding of GR may provide an explanation for the increased GR activity in G6PD deficient red cells.