Evolutionary and functional insights into the mechanism underlying body-size-related adaptation of mammalian hemoglobin.

Hemoglobin (Hb) represents a model protein to study molecular adaptation in vertebrates. Although both affinity and cooperativity of oxygen binding to Hb affect tissue oxygen delivery, only the former was thought to determine molecular adaptations of Hb. Here, we suggest that Hb affinity and cooperativity reflect evolutionary and physiological adaptions that optimized tissue oxygen delivery.

Using the MWC model to describe heterotropic interactions in hemoglobin.

Hemoglobin is a classical model allosteric protein. Research on hemoglobin parallels the development of key cooperativity and allostery concepts, such as the 'all-or-none' Hill formalism, the stepwise Adair binding formulation and the concerted Monod-Wymann-Changuex (MWC) allosteric model. While it is clear that the MWC model adequately describes the cooperative binding of oxygen to hemoglobin, rationalizing the effects of H+, CO2 or organophosphate ligands on hemoglobin-oxygen saturation using the same model remains controversial.