title: A two-state analysis of co-operative oxygen binding in the three human embryonic haemoglobins.
abstract: The binding of oxygen to the three human embryonic haemoglobins, at pH 7.4, has been shown to occur as a co-operative process. Analysis of oxygen-binding curves obtained in the absence of organic phosphate allosteric effectors shows that the process can be described quite accurately by the two-state model of allosteric action. In the presence of organic phosphates, the binding affinity for oxygen to the T-state of the alpha 2 epsilon 2 and zeta 2 epsilon 2 haemoglobins is significantly lowered. The values of the best-fit two-state parameters determined for each of the embryonic haemoglobins together with the temperature-dependence of the overall equilibrium binding process are discussed in terms of oxygen transfer from the maternal blood supply. Fast-reaction studies have been used to determine the rate constants of the oxygen association and dissociation processes occurring in the R-state and the rate of the allosteric R > T conformational transition. Analysis of these data suggests a likely reason for the high affinity and low co-operativity of the embryonic proteins and identifies the origins of the inability of equilibrium measurements to identify chain non-equivalence in the R-state.
authors.affiliation: Biochemistry and Molecular Biology, University of Auckland, New Zealand.
authors.forename: T
authors.initials: T
authors.lastname: Brittain
authors.forename: O M
authors.initials: OM
authors.lastname: Hofmann
authors.forename: N J
authors.initials: NJ
authors.lastname: Watmough
authors.forename: C
authors.initials: C
authors.lastname: Greenwood
authors.forename: R E
authors.initials: RE
authors.lastname: Weber
mesh_terms: D000494:Allosteric Regulation; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D010100:Oxygen / Q000097:blood*; D011247:Pregnancy; D011485:Protein Binding; D013696:Temperature
chemical_list: D005319:Fetal Hemoglobin; D010100:Oxygen