A quantitative model for the cooperative mechanism of human hemoglobin.

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A quantitative model has been developed for the cooperative oxygenation of human hemoglobin. The model correlates the structural and energetic features of ligand-linked subunit interactions within the tetrameric molecule and the coupling of these interactions to the binding of oxygen and Bohr protons. Recent findings are incorporated regarding (i) the sites of regulatory energy change within the tetrameric molecule, (ii) the nature of the Bohr effect for tetramers and dimers, (iii) the fractional Bohr proton release at each stage of oxygenation, (iv) relative probabilities of binding to the alpha and beta chains within the tetramer, and (v) an extensive data base recently obtained on the linked processes of oxygenation, proton binding, and subunit interactions [Chu, A. H., Turner, B. W. & Ackers, G. K. (1984) Biochemistry 23, 604-617]. Least squares minimization was used to evaluate from these data the free energies for the various processes. A special feature of the model lies in the synchronization of Bohr proton release with changes in quaternary structure. This leads to the striking prediction that a major fraction (as much as 30%) of tetramers are in the oxy quaternary structure after the first oxygen is bound. The model provides a rationale for the essential features of regulatory energy control, and it defines several kinds of additional information that are needed for a more complete understanding of the hemoglobin mechanism.

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