Stimulation of the glucose oxidative pathway in human erythrocytes by methylene blue.

Barron and coworkers (l--3) demonstrated nearly 30 years ago that the respiration of non-nucleated erythrocytes may be greatly stimulated by the addition of methylene blue to the buffer system. Explanations for this phenomenon have been given as increased oxidation of a degradation product of glucose (2), oxidation of lactate (4), increased reversible conversion of hemoglobin to methemoglobin (5), and conversion of lactic acid to pyruvate (6). None of these explanations, however, accounted for the magnitude of the increased respiration. From the studies presented here it is proposed that methylene blue activates a cyclic glucose oxidative pathway in mammalian red cells, and that this mechanism accounts for as much as 85 per cent of the oxygen consumed by human erythrocytes in the presence of methylene blue.