Fig. 5
Threshold can shift. The hemoglobin-oxygen binding is a classic example of positive cooperativity and exhibits a sigmoidal curve (red curve). The curve can be shifted rightward (blue curve), representing reduced affinity for oxygen, by elevated temperature, CO2, and 2,3-diphosphoglycerate (DPG), and reduced pH, resulting in increased threshold. Sickle cell hemoglobin (HbSS) and sulfhemoglobin (Sulf-Hb) have reduced affinity to oxygen, so exhibits right-shifted curve. The curve can be shifted leftward (green curve), representing increased affinity for oxygen, by reduced temperature, CO2, and DPG, and elevated pH. Methemoglobinemia (metHb), fetal hemoglobin and CO-bound Hb (CO-Hb) have higher affinity to oxygen, so exhibit leftward curve. These examples demonstrate that the threshold can be shifted by environmental or physiological factors, as well as by changes in the protein structure. Adapted from [128]