Regulatory Mechanism of Glutathione Reductase Activity in Human Red Cells

Abstract

Abstract The mechanism by which glutathione reductase (GR) activity is regulated in relation to flavin metabolism was studied in red cells of normal adults, cord blood, and patients with severe metabolic disorders using spectrophotometric, fluorometric, and radiochemical methods. The increased activity of GR in red cells of adult patients with severe hepatic cirrhosis, chronic uremia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is related to the increased per cent saturation of GR with flavin adenine dinucleotide (FAD), and increased red cell flavin level. The per cent saturation of GR with FAD correlates with (1) the degree of clinical severity in hepatic cirrhosis or chronic uremia, and (2) total flavin level in red cells. Thus, the increased GR activity in these patients may be regulated actively or passively by the increased flavin level in red cells. This suggests that the increased requirement for enhanced activity of the pentose phosphate pathway may affect GR metabolism secondarily, leading to the association of GR with FAD through an increased uptake of riboflavin. In contrast to the results in adult red cells, cord erythrocytes show an unexpected metabolic pattern of GR and flavin metabolism. Although the total GR activity of cord red cells is considerably higher than in adult red cells, cord red cell GR is only partly saturated with FAD even in the presence of a significantly increased flavin level in cord red cells. Thus, cord red cells may have an additional control mechanism of GR activity.