Hemoglobin is also a murzyme mediating oxidative phosphorylation in human erythrocytes
Hemoglobin (Hb) transports oxygen via blood to various cells of the body and it is the most abundant protein found in erythrocytes. Herein, we propose an evidence-based hypothesis that Hb has a hitherto undiscovered function of serving as a murzyme (a redox enzyme working along the principles of murburn concept), catalyzing the synthesis of ATP in RBC, using diffusible reactive oxygen species (DROS). We support our hypothesis with theoretical arguments, earlier experimental findings and in silico explorations. The current work explains earlier reported in situ experimental findings/suggestions of 2,3-bisphosphoglycerate (BPG) and ADP binding at the same locus. We demonstrate that this interaction site is located at the heme cavity entrance with the binding energy in the order of BPG > NADH > ADP ~ ATP > AMP, thereby explaining important physiological outcomes. The findings pose significant implications in routine physiology and pathologies like sickle cell anemia and thalassemia.