The Reduction of Methemoglobin in Erythrocytes of a Patient with Congenital Methemoglobinemia, Subjects with Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency, and Normal Individuals

The pathways for the reduction of methemoglobin to hemoglobin that are dependent upon the generation of reduced pyridine nucleotides were studied in normal human erythrocytes, in erythrocytes deficient in G-6-PD activity and in erythrocytes of a subject with congenital methemoglobinemia. Reduction of methemoglobin, produced by treatment with nitrite, occurred at equivalent rates in normal and G-6-PD deficient erythrocytes, but failed to occur in the erythrocytes of the patient with congenital methemoglobinemia upon incubation with glucose or inosine. The DPNH-utilizing diaphorase-like system was normal in hemolysates of G-6-PD deficient erythrocytes, but was markedly deficient in hemolysates of erythrocytes of the subject with congenital methemoglobinemia. The marked acceleration of methemoglobin reduction that occurred upon the addition of methylene blue to normal erythrocytes and to the erythrocytes of the woman with congenital methemoglobinemia did not occur with G-6-PD deficient erythrocytes. The TPNH-utilizing methemoglobin reductase system was normal in hemolysates of erythrocytes of the patient with congenital methemoglobinemia, but was reduced to about 50 per cent of normal activity in hemolysates of G-6-PD deficient erythrocytes.

The reduction of methemoglobin to hemoglobin in intact normal and G-6-PD deficient human erythrocytes probably proceeds by way of a DPNH-utilizing, diaphorase-like system that is deficient in the erythrocytes of one type of congenital methemoglobinemia. The TPNH-utilizing methemoglobin reductase appears to be a reserve system that requires an artificial electron carrier, such as methylene blue, to become fully effective in reducing methemoglobin to hemoglobin. The TPNH-methemoglobin reductase system is impaired in G-6-PD deficient erythrocytes not only because of a deficient source of TPNH, but, perhaps, also because of a defect in this methemoglobin reductase system itself.