The interaction of proteins with ND may alter their structure and activity.33,48,49 Presumably, if ND interacts extensively with the membrane proteins, it can modify the structure and functionality, including transport proteins involved in oxygen transport. As a result, interaction of ND with the membrane alters oxygen and other important substances concentrations in the RBC cytoplasm. Additionally, it has been already shown that the organic phosphate, i.e., 2,3-diphosphoglycerate (2, 3 DPG) in the RBC, binds with Hb (with -sheets) and affects the Hb affinity to oxygen (oxygen binding capacity), facilitating the detaching from Hb molecule.35 It is important that 2, 3 DPG is involved in the interaction of Hb with membrane, particularly with the band three protein. Thus, varying membrane state can vary conditions of 2, 3 DPG interaction with the membrane; and correspondingly, the interaction between Hb and 2, 3 DPG changes. So, the predominant affinity of 2, 3 DPG to deoxy-Hb relatively oxy-Hb may be one of the reasons why the observed effect of cND on the oxygenation-deoxygenation cycle differs for different oxygenation states.