Redox Potential (E0') of the β-Chain 93Cys of HbS Measured with the Equilibrium Technique in a Heterozygous Sickle Cell Carrier Subject.

The hitherto unknown thiol-disulfide redox potential (E0') of the β93Cys residue in the HbS (β6Glu→Val) variant of human hemoglobin was calculated by MALDI-ToF mass spectrometry, which analyzes blood from a heterozygous carrier. To calculate the (E0') value, a redox equilibrium model was adopted, and the previously calculated value for wild-type β-Hb chain (E0' -121 mV) was used. An E0' value of -130.5 ± 1.7 mV for the β93Cys residue of HbS was obtained, thus a more reducing value than E0' in the wild-type isoform. Glutathionylation from this residue in the HbS tetramer lowers the extent of protein aggregation in fibrils and the clinical consequences, such as painful capillary occlusion and hemolysis. This finding confirmed the peculiar property of HbS as a more reactive scavenger of glutathione sulphinic acid (E0' = -264 mV), which forms in the cytoplasm of red blood cells and reacts with structural and regulatory proteins, including hemoglobin. The ability to assess the erythrocyte oxidative status in sickle cell carriers can be developed into an additional functional test to rationally assess the effect of drug treatment and antioxidant dietary interventions on improving disease control.