title: Free energy changes and components implicit in the MWC allosteric model for the cooperative oxygen binding of hemoglobin.
abstract: Hill's plots of oxygen binding isotherms reveal the presence of a transition between two different oxygen affinities at the beginning and end of the isotherm. They correspond to the two conformations anticipated by the MWC model, namely, the T and R conformations at the beginning and end of oxygen binding, when the lower affinity of the T form develops into the higher affinity of the R form. The difference between the binding Gibbs free energy changes of the two affinities (Δ G(L)) is the free energy of binding cooperativity. Notably, Δ G(L) is positive in favor of the T form, which moves to a higher energy level upon oxygen release. Osmotic stress reveals a higher volume/surface ratio of deoxyhemoglobin, with a positive Δ G(W) also in favor of the T form. An increasing protein concentration shifts the isotherms to the right, indicating the formation of intermediate polymeric forms. The enthalpy of the intermediates shows a strong absorption of heat at the third oxygenation step because of polymer formation with quinary, and higher-order, structures. The disassembly of intermediate polymers releases energy with a negative Δ G that compensates and allows the positive values of Δ G(L). High-energy polymers are the barrier preventing the relaxation of the T and R conformations into one another. The MWC allosteric model is the best justification of oxygen binding cooperativity.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ebucci@umaryland.edu
authors.forename: Enrico
authors.initials: E
authors.lastname: Bucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Pucciarelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Angeletti
mesh_terms: D000495:Allosteric Site; D006454:Hemoglobins / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015233:Models, Statistical; D009995:Osmosis; D010100:Oxygen / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D013053:Spectrophotometry; D013696:Temperature; D013816:Thermodynamics
chemical_list: D006454:Hemoglobins; D011108:Polymers; C100003:deoxyhemoglobin; D010100:Oxygen