A plausible sequence of the conformational changes of hemoglobin induced by oxygenation.

Recent experimental data of oxygen equilibrium constants of human adult hemoglobin, which are measured over a wide range of oxygen pressures, are analyzed successfully from the viewpoint that the change in the molecular structure of hemoglobin induced by oxygenation is considered individually at each stage of oxygenation. Then, a simple phenomenological rule, which explains quantitatively the values of the four Adair constants with only three parameters, is found for hemoglobin under normal physiological conditions. The temperature dependence of these parameters suggests a sequence of the conformational changes such that until the third stage of oxygenation the conformational changes occur within the deoxy quaternary structure and at the fourth stage of oxygenation the deoxy quaternary structure is altered to the oxy one. The effects of pH and phosphate compounds on the Adair constants are discussed, and a possible modification and extension of the rule is suggested. The connection between the rule and the molecular structures of deoxy- and oxyhemoglobin is also discussed.