A combined system for the study of glutathione metabolism in erythrocytes

Abstract

A combined system for measuring glutathione stability, hexose monophosphate shunt activity, glycine incorporation into glutathione, glucose consumption and lactate formation in erythrocytes has been devised. In severe glucose-6-phosphate dehydrogenase deficiency associated with chronic hemolytic anemia, extremely small amounts of glucose were metabolized via the hexose monophosphate shunt, glutathione stability decreased, and glycine incorporation into glutathione increased. However, in mild glucose-6-phosphate dehydrogenase deficiency with no clinical manifestation, glutathione stability and recycling via the hexose monophosphate shunt decreased and hexose monophosphate shunt activity decreased slightly. In glucosephosphate isomerase deficiency, more than half of glucose was metabolized via the hexose monophosphate shunt, while Embden-Meyerhof pathway activity and recycling via the hexose monophosphate shunt decreased. In a splenectomized patient with pyruvate kinase deficiency with reticulocytosis, high hexose monophosphate shunt activity, glucose consumption and lactate formation were observed; but in pyruvate kinase deficiency without splenectomy, decreased glutathione stability, low glucose consumption and lactate formation were observed. These results indicate that one abnormal enzyme may exert its influence on several enzyme systems and that it is valuable to investigate the metabolism of erythrocytes using this system in different enzymopathies as well as different variants of one enzyme deficiency.