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Mechanisms Regulating the Reactions of Human Hemoglobin with Oxygen and Carbon Monoxide

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Clinical Aspects of O2 Transport and Tissue Oxygenation

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Abstract

The reactions of hemoglobin with oxygen and carbon monoxide are subject to regulation by the heme and the residues surrounding it and by the effectors, also known as heterotopic ligands (H+, Cl-, CO2, and 2,3-diphosphoglycerate), that regulate the equilibrium between its two forms, the oxy or R-structure with high and the deoxy or T-structure with low oxygen affinity. The stereochemical mechanisms of regulation have been studied for many years using a variety of methods. What is new since the subject was last surveyed [1] is determination of the crystal structures at resolutions sufficient to resolve individual atoms of the heme and its surroundings; such structures have now been determined for deoxy, oxy, and carbon monoxyhemoglobin, and for several analogues of transition states in the reaction with oxygen and carbon monoxide. In the past much useful information about the stereochemical mechanism of hemoglobin has come from the study of abnormal human hemoglobins. Now that the genes for the α and ß chains of hemoglobin and for the single chain of myoglobin have been cloned in E. coli, directed mutagenesis has provided new tools for probing the reactions of these proteins with ligands. Finally, an (unsuccessful) search for possible antisickling drugs has led to the discovery of a family of compounds which are more powerful allosteric effectors than the natural one, 2,3-diphosphoglycerate, and combine with sites that are far removed from the diphosphoglycerate binding site.

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  1. M. F. Perutz
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  1. Universitätsklinikum Steglitz Klinik für Anästhesiologie und Operative Intensivmedizin, Freie Universität Berlin, Hindenburgdamm 30, 1000, Berlin 45, Germany

    K. Reinhart  & K. Eyrich  & 

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© 1989 Springer-Verlag Berlin Heidelberg

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Perutz, M.F. (1989). Mechanisms Regulating the Reactions of Human Hemoglobin with Oxygen and Carbon Monoxide. In: Reinhart, K., Eyrich, K. (eds) Clinical Aspects of O2 Transport and Tissue Oxygenation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83872-9_1

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  • DOI: https://doi.org/10.1007/978-3-642-83872-9_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-51470-1

  • Online ISBN: 978-3-642-83872-9

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