Abstract
Hardly any molecule has attracted the interest of as many scientific disciplines as has haemoglobin. Contributions from physicists, chemists and biologists have combined to bring about a full understanding of the relationship between its structure and function. In particular, the finding that red cell metabolism and haemoglobin function are interdependent has provided important biological insights that have transformed the red cell from a seemingly inconspicuous biological unit into a model demonstrating several fundamental biological principles.
It is the aim of this article to summarise current knowledge about the physiological properties of haemoglobin in transport of oxygen and carbon dioxide in the blood, and to relate this to its molecular structure.
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Adair, G. S.: Thermodynamical proof of the reciprocal relationship of oxygen and carbon dioxide in blood. J. Physiol. (Lond.) 58, IV–VP (1923).
Adamson, J. W., Parer, J. T., Stamatoyannopoulos, G.: Erythrocytosis associated with hemoglobin Rainier: Oxygen equilibria and marrow regulation. J. clin. Invest. 48, 1376–1386 (1969).
Antonini, E.: Interrelationship between structure and function in hemoglobin and myoglobin. Physiol. Rev. 45, 123–170 (1965).
Antonini, E., Brunori, M.: Hemoglobin and myoglobin in their reactions with ligands. Amsterdam-London: North-Holland Publ. Comp. 1971.
Antonini, E., Schuster, T. M., Brunori, M., Wyman, J.: The kinetics of the Bohr effect in the reaction of human hemoglobin with carbon monoxide. J. biol. Chem. 240, PC 2262–PC 2264 (1965a).
Antonini, E., Wyman, J., Brunori, M., Bucci, E., Fronticelli, C., Rossi-Fanelli, A.: Studies on the relations between molecular and functional properties of hemoglobin. IV. The Bohr effect in human hemoglobin measured by proton binding. J. biol. Chem. 238, 2950–2957 (1963).
Antonini, E., Wyman, J., Brunori, M., Fronticelli, C., Bucci, E., Rossi-Fanelli, A.: Studies on the relations between molecular and functional properties of hemoglobin. V. The influence of temperature on the Bohr effect in human and horse hemoglobin. J. biol. Chem. 240, 1096–1103 (1965b).
Arnone, A.: X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhaemoglobin. Nature (Lond.) 237, 146–149 (1972).
Asakura, T., Sato, S., Minakami, S., Yoshikawa, H.: Effect of deoxygenation of intracellular hemoglobin on red cell glycolysis. J. Biochem. 59, 524–526 (1966).
Aste-Salazar, H., Hurtado, A.: The affinity of hemoglobin for oxygen at sea level and at high altitudes. Amer. J. Physiol. 142, 733–743 (1944).
Astrup, P., Engel, K., Severinghaus, J. W., Munson, E.: The influence of temperature and pH on the dissociation curve of oxyhemoglobin of human blood. Scand. J. clin. Lab. Invest. 17, 515–523 (1965).
Bailey, J. E., Beetlestone, J. G., Irvine, D. H.: Reactivity differences between haemoglobins. Part XVII. The variability of the Bohr effect between species and the effect of 2,3-diphosphoglyceric acid on the Bohr effect. J. chem. Soc. (A) 5, 756–762 (1970).
Banchero, N., Grover, R. F.: Effect of different levels of simulated altitude on O2 transport in llama and sheep. Amer. J. Physiol. 222, 1239–1245 (1972).
Banerjee, R., Alpert, Y., Leterrier, F., Williams, R. J. P.: Visible absorption and electron spin resonance spectra of the isolated chains of human hemoglobin. Discussion of chain-mediated heme-heme interaction. Biochemistry 8, 2862–2867 (1969).
Banerjee, R., Cassoly, R.: Oxygen equilibria of human hemoglobin valency hybrids. Discussion on the intrinsic properties of α-and β-chains in the native protein. J. Mol. Biol. 42, 351–361 (1969).
Banerjee, R., Stetzkowski, F., Henry, Y.: Reciprocal effects of change of subunit structure on ligand equilibria of haemoglobin valency hybrids. Attempted correlation with Electron Paramagnetic Resonance Spectra. J. Mol. Biol. 73, 455–467 (1973).
Barcroft, J.: The respiratory function of blood. II. Haemoglobin. Cambridge: Cambridge University Press 1928.
Bartels, H.: Chemical factors affecting oxygen carriage and transfer from maternal to foetal blood. In: Oxygen supply to the human foetus. Oxford: Blackwell 1959.
Bartels, H.: Comparative physiology of oxygen transport in mammals. Lancet 19, 599–604 (1964).
Bartels, H., Hilpert, P., Riegel, K.: Gaswechsel und Herzzeitvolumen während der ersten Lebenswochen. Pflügers Arch. 277, 61–75 (1963).
Battaglia, F. C., McGaughey, H., Makowski, E. L., Meschia, G.: Postnatal changes in oxygen affinity of sheep red cells: a dual role of diphosphoglyceric acid. Amer. J. Physiol. 219, 217–221 (1970).
Bauer, C.: Antagonistic influence of CO2 and 2,3-diphosphoglycerate on the Bohr effect of human haemoglobin. Life Sci. (II) 8, 1041–1046 (1969).
Bauer, C.: Reduction of the carbon dioxide affinity of human haemoglobin solutions by 2,3-diphosphoglycerate. Resp. Physiol. 10, 10–19 (1970).
Bauer, C., Henry, Y., Banerjee, R.: Binding of 2,3-diphosphoglycerate to haemoglobin valency hybrids. Nature (New Biol.) 242, 208–209 (1973).
Bauer, C., Ludwig, I., Ludwig, M.: Different effects of 2,3-diphosphoglycerate and adenosine triphosphate on the oxygen affinity of human adult and foetal haemoglobin. Life Sci. (I) 7, 1339–1343 (1968).
Bauer, C., Ludwig, M., Ludwig, I., Bartels, H.: Factors governing the oxygen affinity of human adult and foetal blood. Resp. Physiol. 7, 271–277 (1969).
Bauer, C., Schröder, E.: Carbamino compounds of haemoglobin in human adult and foetal blood. J. Physiol. (Lond.) 227, 457–471 (1972).
Baumann, R., Bauer, C., Bartels, H.: Influence of chronic and acute hypoxia on oxygen affinity and red cell 2,3-diphosphoglycerate of rats and guinea pigs. Resp. Physiol. 11, 135–144 (1971).
Bellingham, A. J.: The physiological significance of the Hill parameter “n”. Scand. J. Haemat. 9, 552–556 (1972).
Bellingham, A. J., Detter, J. C., Lenfant, C.: Regulatory mechanisms of hemoglobin oxygen affinity in acidosis and alkalosis. J. clin. Invest. 50, 700–706 (1971).
Bellingham, A. J., Huehns, E. R.: Compensation in haemolytic anaemias caused by abnormal haemoglobins. Nature (Lond.) 218, 924–926 (1968).
Benesch, R., Benesch, R. E.: The chemistry of the Bohr effect. I. The reaction of N-ethylmaleimide with oxygen linked acid groups of hemoglobin. J. biol. Chem. 236, 405–410 (1961).
Benesch, R., Benesch, R. E.: Some relations between structure and function in hemoglobin. J. Mol. Biol. 6, 498–505 (1963).
Benesch, R., Benesch, R. E.: The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin. Biochem. Biophys. Res. Commun. 26, 162–167 (1967).
Benesch, R., Benesch, R. E., Enoki, Y.: The interaction of hemoglobin and its subunits with 2,3-diphosphoglycerate. Proc. nat. Acad. Sci. (Wash.) 59, 1102–1106 (1968a).
Benesch, R., Benesch, R. E., Yu, C. I.: Reciprocal binding of oxygen and diphosphoglycerate by human hemoglobin. Proc. nat. Acad. Sci. (Wash.) 59, 526–532 (1968b).
Benesch, R. E., Benesch, R., Bank, A., Renthal, R., Bray, B. A.: The preparation and properties of pyridoxilated hemoglobin. In: Genetical, functional and physical studies of hemoglobin. Basel: Karger 1971.
Benesch, R. E., Benesch, R., Renthal, R., Maeda, N.: Affinity labeling of the polyphosphate binding site of hemoglobin. Biochemistry 11, 3576–3582 (1972).
Benesch, R. E., Benesch, R., Yu, C. I.: The oxygenation of hemoglobin in the presence of 2,3-diphosphoglycerate. Effect of temperature, pH, ionic strength and hemoglobin concentration. Biochemistry 8, 2567–2571 (1969).
Benesch, R. E., Ranney, H., Benesch, R., Smith, G. M.: The chemistry of the Bohr effect. II. Some properties of hemoglobin H. J. biol. Chem. 236, 2926–2929 (1961).
Bohr, C.: Theoretische Behandlung der quantitativen Verhältnisse bei der Sauerstoffaufnahme des Hämoglobins. Zbl. Physiol. 17, 682–691 (1903).
Bohr, C., Hasselbalch, K., Krogh, A.: Über einen in biologischer Beziehung wichtigen Ein-fluß, den die Kohlensäurespannung des Blutes auf dessen Sauerstoffspannung übt. Scand. Arch. Physiol. 16, 402–412 (1904).
Bolton, W., Perutz, M. F.: Three dimensional Fourier synthesis of horse deoxyhaemoglobin at 2.8 Å resolution. Nature (Lond.) 228, 551–552 (1970).
Braunitzer, G.: Die Primärstruktur der Eiweißstoffe. Verh. Ges. dtsch. Naturf. u. Ärz. 54, 407–417 (1967).
Braunitzer, G., Hilse, K., Rudloff, V., Hilschmann, N.: The hemoglobins. Adv. Protein Chem. 19, 1–71 (1964).
Brenna, O., Luzzana, M., Pace, M., Perrella, M., Rossi, F., Rossi-Bernardi, L., Roughton, F. J. W.: The interaction between hemoglobin and its oxygen-linked ligands. In: Hemoglobin and red cell structure and function. New York-London: Plenum Press 1972.
Bruin de, S. H., Janssen, L. H. M.: The interaction of 2,3-diphosphoglycerate with human hemoglobin. Effects on the alkaline and acid Bohr effect. J. biol. Chem. 248, 2774–2777 (1973).
Bruin de, S. H., Janssen, L. H. M., van Os, G.A.J.: Effect of 2,3-diphosphoglycerate on the Bohr effect of human adult hemoglobin. Biochem. Biophys. Res. Commun. 45, 544–550 (1971).
Brunori, M., Amiconi, G., Antonini, E., Wyman, J., Winterhalter, K. H.: Artificial intermediates in the reaction of haemoglobin. Functional and conformational properties of the cyanmet intermediates. J. Mol. Biol. 49, 461–471 (1970).
Bunn, H. F., Briehl, R. W.: The interaction of 2,3-diphosphoglycerate with various human hemoglobins. J. clin. Invest. 49, 1088–1095 (1970).
Bunn, H. F., Guidotti, G.: Stabilizing interactions in hemoglobin. J. biol. Chem. 247, 2345–2350 (1972).
Caldwell, P. R. B., Nagel, R. L., Jaffé, E. R.: The effect of oxygen, carbon dioxide, pH and cyanate on the binding of 2,3-diphospholgycerate to human hemoglobin. Biochem. Biophys. Res. Commun. 44, 1504–1509 (1971).
Cassoly, R., Gibson, Q. H.: The kinetics of ligand binding to hemoglobin valency hybrids and the effect of anions. J. biol. Chem. 247, 7332–7341 (1972).
Chanutin, A., Curnish, R. R.: Effect of organic and inorganic phosphate on the oxygen equilibrium of human erythrocytes. Arch. Biochem. Biophys. 121, 96–102 (1967).
Christiansen, J., Douglas, C. G., Haldane, J. S.: The absorption and dissociation of carbon dioxide by human blood. J. Physiol. (Lond.) 48, 244–271 (1914).
Coburn, R. F., Mayers, L. B.: Myoglobin oxygen tension determined from measurements of carboxymyoglobin in sceletal muscle. Amer. J. Physiol. 220, 66–74 (1971).
Coburn, R. F., Ploegmakers, F., Gondrie, P., Abboud, R.: Myocardial myoglobin oxygen tension. Amer. J. Physiol. 224, 870–876 (1973).
Deal, W. J., Mohlman, S. G., Sprang, M. L.: Conformational equilibria in spin-labeled hemoglobin. Science 171, 1147–1149 (1970).
Delivoria-Papadopoulos, M., Oski, F. A., Gottlieb, A. J.: Oxygen-hemoglobin dissociation curves. Effect of inherited enzyme defects of the red cell. Science 165, 601–602 (1969).
Dill, D. B., Forbes, W. H.: Respiratory and metabolic effects of hypothermia. Amer. J. Physiol. 132, 685–697 (1941).
Dill, D. B., Graybiel, A., Hurtado, A., Taquini, A. C.: Der Gasaustausch in der Lunge im Alter. Z. Alternsforsch. 2, 20–33 and 172 (1940).
Doll, E., Keul, J., Maiwald, C.: Oxygen tension and acid-base equilibria in venous blood of working muscle. Amer. J. Physiol. 215, 23–29 (1968).
Duhm, J.: Effects of 2,3-diphosphoglycerate and other organic phosphate compounds on oxygen affinity and intracellular pH of human erythrocytes. Pflügers Arch. 326, 341–356 (1971).
Duhm, J.: 2,3-diphosphoglycerate metabolism of erythrocytes and oxygen transport function. In: Erythrocytes, Thrombocytes, Leucocytes. Stuttgart: Thieme 1973.
Duhm, J., Gerlach, E.: On the mechanism of the hypoxia induced increase of 2,3-diphosphoglycerate in erythrocytes. Pflügers Arch. 326, 254–269 (1971).
Eaton, J. W., Brewer, G. J.: The relationship between red cell 2,3-diphosphoglycerate and levels of hemoglobin in the human. Proc. nat. Acad. Sci. (Wash.) 61, 756–760 (1968).
Edelstein, S. J.: Extensions of the allosteric model for haemoglobin. Nature (Lond.) 230, 224–227 (1971).
Faurhault, C.: Études sur les solutions aqueuses de carbamates et de carbonates. J. Chim. Phys. 22, 1–44 (1925).
Ferguson, J. K. W.: Carbamino compounds of CO2 with human haemoglobin and their role in the transport of CO2. J. Physiol. (Lond.) 88, 40–55 (1936).
Ferguson, J. K. W., Roughton, F. J. W.: The direct chemical estimation of carbamino compounds of CO2 with haemoglobin. J. Physiol. (Lond.) 83, 68–86 (1934a).
Ferguson, J. K. W., Roughton, F. J. W.: The chemical relationships and physiological importance of carbamino compounds of CO2 with haemoglobin. J. Physiol. (Lond.) 83, 87–102 (1934b).
Ferry, R. M., Green, A. A.: Studies in the chemistry of hemoglobin. III. The equilibrium between oxygen and hemoglobin and its relation to changing hydrogen ion activity. J. biol. Chem. 81, 175–203 (1929).
Forster, R. E., Constantine, H. P., Craw, M. R., Rotman, H. H., Klocke, R. A.: Reaction of CO2 with human hemoglobin solution. J. biol. Chem. 243, 3317–3326 (1968).
Garby, L., de Verdier, D. H.: Affinity of human hemoglobin A to 2,3-diphosphoglycerate. Effect of hemoglobin concentration and of pH. Scand. J. clin. Lab. Invest. 27, 345–350 (1971).
Garby, L., Robert, M., Zaar, B.: Proton-and carbamino-linked oxygen affinity of normal human blood. Acta Physiol. Scand. 84, 482–492 (1972).
German, B., Wyman, J.: The titration curves of oxygenated and reduced haemoglobin. J. biol. Chem. 117, 533–550 (1937).
Gersonde, K., Overkamp, M., Sick, H., Trittelvitz, E., Junge, W.: β-chain allostery in the frozen quaternary T-structure of haemoglobin M Iwate. Eur. J. Biochem. In press (1973).
Gibson, Q. H.: The contribution of the α-and β-chains to the kinetics of oxygen binding to and dissociation from hemoglobin. Proc. nat. Acad. Sci. (Wash.) 70, 1–4 (1973).
Gray, R. D.: The kinetics of the alkaline Bohr effect of human hemoglobin. J. biol. Chem. 245, 2914–2921 (1970).
Haber, J. E., Koshland, D. E.: The effect of 2,3-diphosphoglyceric acid on the changes in β-β interactions in hemoglobin during oxygenation. J. biol. Chem. 246, 7790–7793 (1971).
Harms, H., Bartels, H.: CO2-Dissoziationskurven des menschlichen Blutes bei Ternperaturen von 5 37° C bei unterschiedlicher O2-Sättigung. Pflügers Arch. 272, 384–392 (1961).
Hartley, L. H.: Adjustments of the oxygen transport system during residence at high altitude. In: Hemoglobin and red cell structure and function. New York-London: Plenum Press 1972.
Hastings, A. B., van Slyke, D. D., Neill, J. M., Heidelberger, M., Harington, C. R.: Studies of gas and electrolyte equilibria in blood. IV. The acid properties of reduced and oxygenated hemoglobin. J. biol. Chem. 60, 89–100 (1924).
Haurowitz, F.: Das Gleichgewicht zwischen Hämoglobin und Sauerstoff. Z. physiol. Chem. 254, 266–274 (1938).
Hayashi, A., Suzuki, T., Shimizu, A., Yamamura, Y.: Properties of hemoglobin M. Unequi-valent nature of the α-and β-subunits in the hemoglobin molecule. Biochim. Biophys. Acta 168, 262–273 (1968).
Henriques, O. M.: Die Bindungsweise des Kohlendioxyds im Blut. I. Über die Geschwindigkeit der Anhydrierung bzw. der Hydratisierung der Kohlens äurekomponenten im Blut. Biochem. Z. 200, 1–9 (1928).
Henriques, O. M.: Über Carbhämoglobin. Ergeb. Physiol. 28, 625–689 (1929).
Henry, Y., Banerjee, R.: Electron paramagnetic studies of nitric oxide haemoglobin derivatives: Isolated subunits and nitric oxide hybrids. J. Mol. Biol. 73, 469–482 (1973).
Henry, Y., Cassoly, R.: Chain non-equivalence in nitric oxide binding to hemoglobin. Biochem. Biophys. Res. Commun. 51, 659–665 (1973).
Hermann, H., Hudoffsky, B., Netter, H., Travia, L.: Über den spezifischen Einfluß der Kohlensäure auf die Sauerstoffbindungskurve des H ämoglobins. Pflügers Arch. 242, 311–327 (1939).
Herzfeld, J., Stanley, H. E.: A general model of cooperativity and its application to DPG inhibition of hemoglobin oxygenation. Biochem. Biophys. Res. Commun. 48, 307–313 (1972).
Hill, A. V.: The possible effects of aggregation of the molecules of haemoglobin on its dissociation curve. J. Physiol. (Lond.) 40, IV–VII (1910).
Hill, R. J., Davis, R. W.: The pK of specific groups of proteins. I. The α-amino group of the α-chain of human CO hemoglobin. J. biol. Chem. 242, 2005–2012 (1967).
Hill, E. P., Power, G. G., Longo, L. D.: A mathematical model of carbon dioxide transfer in the placenta and its interaction with oxygen. Amer. J. Physiol. 224, 283–299 (1973).
Hoard, J. L.: Stereochemistry of porphyrins. In: Hemes and hemoproteins. New York-London: Academic Press 1966.
Hopfield, J. J., Shulman, R. G., Ogawa, S.: An allosteric model of hemoglobin: I, Kinetics. J. Mol. Biol. 61, 425–443 (1971).
Huestis, W. H., Raftery, M. A.: 19F-NMR studies of oxygen binding to hemoglobin. Biochem. Biophys. Res. Commun. 49, 1358–1365 (1972).
Johansen, K., Lenfant, C.: A comparative approach to the adaptability of O2-Hb affinity. In: Oxygen affinity of hemoglobin and red cell acid base status. Copenhagen: Munksgaard 1972.
Kendrew, J. C., Dickerson, R. E., Straudberg, B. E., Hart, R. G., Davis, D. R., Phillips, D. C., Shore, V. C.: Structure of myoglobin. A three-dimensional Fourier synthesis at 2 Å resolution. Nature (Lond.) 185, 422–427 (1960).
Keys, A., Hall, F. G., Guzman Barron, E. S.: The position of the oxygen dissociation curve of human blood at high altitude. Amer. J. Physioi. 115, 292–307 (1936).
Kilmartin, J. V., Breen, J. J., Roberts, G. C. K., Ho, C.: Direct measurement of the pK values of an alkaline Bohr group in human haemoglobin. Proc. nat. Acad. Sci. (Wash.) 70, 1246–1249 (1973).
Kilmartin, J. V., Hewitt, J. A.: The effect of removal of C-terminal residues on cooperative interactions in hemoglobin. Cold Spring Harbor Symp. Quant. Biol. 36, 311–314 (1971).
Kilmartin, J. V., Rossi-Bernardi, L.: Inhibition of CO2 combination and reduction of the Bohr effect in haemoglobin chemically modified at its α-amino groups. Nature (Lond.) 222, 1243–1246 (1969).
Kilmarttn, J. V., Rossi-Bernardi, L.: The binding of carbon dioxide by horse haemoglobin. Biochem. J. 124, 31–45 (1971).
Kilmartin, J. V., Wootton, J. F.: Inhibition of Bohr effect after removal of C-terminal histi-dines from haemoglobin β-chains. Nature (Lond.) 228, 766–767 (1970).
Klinger, R. G., Zahn, D. P., Brox, D. H., Frunder, H. E.: Interaction of hemoglobin with ions. Binding of ATP to human hemoglobin under simulated in vivo conditions. Eur. J. Biochem. 18, 171–177 (1971).
Klocke, R. A.: Mechanism and kinetics of the Haldane effect in human erythrocytes. J. appl. Physiol. In press (1973).
Koshland, D. E., Nemethy, G., Filmer, D.: Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5, 365–385 (1966).
Kreuzer, F., Roughton, F. J. W., Rossi-Bernardi, L., Kernohan, J. C.: Specific effect of CO2 and bicarbonate on the affinity of hemoglobin for oxygen. In: Oxygen affinity of hemoglobin and red cell acid base status. Copenhagen: Munksgaard 1972.
Lenfant, C., Torrance, J., English, E., Finch, C. A., Reynafarje, C., Ramos, J., Faura, J.: Effect of altitude on oxygen binding by hemoglobin and on organic phosphate level. J. clin. Invest. 47, 2652–2656 (1968).
Lenfant, C., Torrance, J., Reynafarje, C.: Shift of the O2-Hb dissociation curve at altitude; mechanism and effect. J. appl. Physiol. 30, 625–631 (1971).
Lindstrom, T. R., Ho, C.: Functional nonequivalence of a and β hemes in human adult hemoglobin. Proc. nat. Acad. Sci. (Wash.) 69, 1707–1710 (1972).
Lindstrom, T. R., Olson, J. S., Mock, N. H., Gibson, Q. H., Ho, C.: Nuclear magnetic resonance studies of hemoglobin. VIII. Evidence for preferential ligand binding to β-chains within deoxyhemoglobins. Biochem. Biophys. Res. Commun. 45, 22–26 (1971).
Lo, H. H., Schimmel, P. R.: Interaction of human hemoglobin with adenine nucleotides. J. boil Chem. 244, 5084–5086 (1969).
Lübbers, D. W., Luff, U. C., Thews, G., Witzleb, E.: Oxygen transport in blood and tissue. Stuttgart: Thieme 1971.
MacQuarrie, R., Gibson, Q. H.: Use of a fluorescent analogue of 2,3-diphosphoglycerate as a probe of human hemoglobin conformation during carbon monoxide binding. J. biol. Chem. 246, 5832–5856 (1971).
Marées de, H., Barbey, K.: Änderung der peripheren Durchblutung durch Ausdauertraining. Z. Kardiol. 62, 653–663 (1973).
Margaria, R., Green, A. A.: The first dissociation constant, pK, of carbonic acid in hemoglobin solutions and its relation to the existence of a combination of hemoglobin with carbon dioxide. J. biol. Chem. 102, 611–634 (1933).
McDonald, M. J., Noble, R. W.: The effect of pH on the rates of ligand replacement reactions of human adult and foetal hemoglobins and their subunits. J. biol. Chem. 247, 4282–4287 (1972).
Metcalfe, J., Dhindsa, D. S.: The physiological effects of displacements of the oxygen dissociation curve. In: Oxygen affinity of hemoglobin and red cell acid base status. Copenhagen: Munksgaard 1972.
Miller, M. E., Rørth, M., Parving, H. H., Howard, D., Reddington, I., Valeri, C. R., Stohlman, F.: pH effect on erythropietin response to hypoxia. N. Engl. J. Med. 288, 706–710 (1973).
Monod, J., Changeux, J.-P., Jacob, F.: Allosteric proteins and cellular control systems. J. Mol. Biol. 6, 306–329 (1963).
Monod, J., Jacob, F.: General conclusions: Teleonomic mechanisms in cellular metabolism, growth and differentiation. Cold Spring Harbor Symp. Quant. Biol. 26, 389–401 (1961).
Monod, J., Wyman, J., Changeux, J.-P.: On the nature of allosteric transitions: A plausible model. J. Mol. Biol. 12, 88–118 (1965).
Moore, L. G., Brewer, G. J., Oelschlegel, F. J.: Red cell metabolic changes in acute and in chronic exposure to high altitude. In: Hemoglobin and red cell structure and function. New York-London: Plenum Press 1972.
Morrow, J. S., Keim, P., Visscher, R. B., Marshall, R. C., Gurd, F. R. N.: Interaction of 13CO2 and bicarbonate with human hemoglobin preparations. Proc. nat. Acad. Sci. (Wash.) 70, 1414–1418 (1973).
Muirhaed, H., Cox, J. M., Mazzarella, L., Perutz, M. F.: Structure and function of haemoglobin. III. A three dimensional Fourier synthesis of human deoxyhaemoglobin at 5.5 Å resolution. J. Mol. Biol. 28, 117–156 (1967).
Muirhaed, H., Greer, J.: Three dimensional Fourier synthesis of human deoxyhaemoglobin at 3. 5 A resolution. Nature (Lond.) 228, 516–519 (1970).
Muirhaed, H., Perutz, M. F.: Structure of haemoglobin. A three dimensional Fourier synthesis of reduced human haemoglobin at 5.5 A resolution. Nature (Lond.) 199, 633–638 (1963).
Niesel, W.: Die Umlagerungshypothese. Ein Beitrag zur Klärung der Sauerstoff-Hämoglobin-Reaktion. Inauguraldissertation, Kiel (1961).
Now, M. J., Edwards, M. J., Metcalfe, J.: Hemoglobin Yakima: II. High blood oxygen affinity associated with compensatory erythrocytosis and normal haemodynamics. J. clin. Invest. 46, 1848–1854 (1967).
Olson, J. S., Gibson, Q. H.: The release of protons and anions during ligand binding to human deoxyhemoglobin. J. biol. Chem. 248, 1623–1630 (1973a).
Olson, J. S., Gibson, Q. H.: The effects of pH and anions on the properties of the α-and β-chains within human deoxyhemoglobin. J. biol. Chem. 248, 1616–1622 (1973b).
Ogata, R. T., McConnell, H. M.: The binding of a spin-labeled triphosphate to hemoglobin. Cold Spring Harbor Symp. Quant. Biol. 36, 325–335 (1971).
Ogata, R. T., McConnell, H. M.: Mechanism of cooperative oxygen binding to hemoglobin. Proc. nat. Acad. Sci. (Wash.) 69, 335–339 (1972a).
Ogata, R. T., McConnell, H. M.: States of hemoglobin in solution. Biochemistry 11, 4792–4799 (1972b).
Ogawa, S., McConnell, H. M.: Spin-label study of hemoglobin conformations in solution. Proc. nat. Acad. Sci. (Wash.) 58, 19–26 (1967).
Oski, F. A., Gottlieb, A. J., Delivoria-Papadopoulos, M., Miller, W. W.: Red cell 2,3-diphosphoglycerate levels in subjects with chronic hypoxemia. N. Engl. J. Med. 280, 1165–1166 (1969).
Oski, F. A., Marshall, B. E., Cohen, P. J., Sugarman, H. J., Miller, L. D.: Exercise with anemia. The role of the left-shifted or right-shifted oxygen-hemoglobin equilibrium curve. Ann. intern. Med. 74, 44–46 (1971).
Pace, M., Rossi-Bernardi, L., Roughton, F. J. W.: The effect of organic phosphates on the reactions of haemoglobin and oxyhaemoglobin (carboxy haemoglobin) with carbon dioxide. Biochem. J. 119, 67–68P (1970).
Parer, J. T.: Oxygen transport in human subjects with hemoglobin variants having altered oxygen affinity. Resp. Physiol. 9, 43–49 (1970).
Parer, J. T., Jones, W. D., Metcalfe, J.: A quantitative comparison of oxygen transport in sheep and human subjects. Resp. Physiol. 2, 196–206 (1967).
Pauling, L.: The oxygen equilibrium of hemoglobin and its structural interpretation. Proc. nat. Acad. Sci. (Wash.) 21, 186–191 (1935).
Perutz, M. F.: Structure and function of haemoglobin. I. A tentative atomic model of horse oxyhaemoglobin. J. Mol. Biol. 13, 646–668 (1965).
Perutz, M. F.: Stereochemistry of cooperative effects in haemoglobin. Nature (Lond.) 228, 726–739 (1970).
Perutz, M. F.: Nature of haem-haem interaction. Nature (Lond.) 237, 495–499 (1972).
Perutz, M. F., Bolton, W., Diamond, R., Muirhaed, H., Watson, H. C.: Structure of haemoglobin. An X-ray examination of reduced horse haemoglobin. Nature (Lond.) 203, 687–690 (1964).
Perutz, M. F., Lehmann, H.: Molecular pathology of human haemoglobin. Nature (Lond.) 219, 902–909 (1968).
Perutz, M. F., Mazzarella, L.: A preliminary X-ray analysis of haemoglobin H. Nature (Lond.) 199, 639 (1963).
Perutz, M. F., Muirhaed, H., Cox, J. M., Goaman, L. C. G.: Three dimensional Fourier synthesis of horse oxyhaemoglobin at 2.8 Å resolution: the atomic model. Nature (Lond.) 219, 131–139 (1968).
Perutz, M. F., Muirhaed, H., Mazzarella, L., Crowther, R. A., Greer, J., Kilmartin, J. V.: Identification of residues responsible for the alkaline Bohr effect in haemoglobin. Nature (Lond.) 222, 1240–1243 (1969).
Perutz, M. F., Rossman, M. G., Cullis, A. F., Mutrhaed, H., Will, G., North, A. C. T.: Structure of haemoglobin. A three dimensional Fourier synthesis at 5.5 A resolution obtained by X-ray analysis. Nature (Lond.) 185, 416–422 (1960).
Rapoport, S.: Regulation of concentration of DPG and ATP in red blood cells. Försvarsmedicin 5, 168–174 (1969).
Rapoport, S., Guest, G. M.: Distribution of acid-soluble posphorus in the blood cells of various vertebrates. J. biol. Chem. 138, 269–282 (1941).
Rapoport, S., Maretzki, D., Schewe, C., Jacobasch, G.: Control of glycolysis in the erythro-cyte on the level of 1,3 DPG. In: Oxygen affinity of hemoglobin and red cell acid base status. Copenhagen: Munksgaard 1972.
Renthal, R., Benesch, R. E., Benesch, R., Bray, B. A.: Affinity labeling of the polyphosphate binding site in hemoglobin with pyridoxal phosphate (PLP). Fed. Proc. 29, 732 (1970).
Richardson, T. Q., Guyton, A. C.: Effects of polycythemia and anemia on cardiac output and other circulatory factors. Amer. J. Physiol. 197, 1167–1170 (1959).
Riegel, K. P.: Respiratory gas transport characteristics of blood and hemoglobin. In: Physiology of the perinatal period. Vol. I. New York: Appleton-Century-Crofts 1970.
Riggs, A.: Functional properties of hemoglobins. Physiol. Rev. 45, 619–673 (1965).
Riggs, A.: Mechanism of the enhancement of the Bohr effect in mammalian hemoglobins by diphosphoglycerate. Proc. nat. Acad. Sci. (Wash.) 68, 2062–2065 (1971).
Rørth, M.: Dependency on acid-base status of blood of oxyhemoglobin dissociation and 2,3-diphosphoglycerate level in human erythrocytes. I. In vitro studies on reduced and oxygenated blood. Scand. J. clin. Lab. Invest. 26, 43–47 (1970).
Rørth, M.: Hemoglobin interactions and red cell metabolism. Copenhagen: Thesis (1973).
RøRTH, M., Nygaard, S. F., Parvtng, H. H.: Red cell metabolism and oxygen affinity of healthy individuals during exposure to high altitude. In: Hemoglobin and red cell structure and function. New York-London: Plenum Press 1972.
Rossi-Bernardi, L., Roughton, F. J. W.: The specific influence of carbon dioxide and carba-mate compounds on the buffer power and Bohr effects in human haemoglobin solutions. J. Physiol. (Lond.) 189, 1–29 (1967).
Roughton, F. J. W.: Transport of oxygen and carbon dioxide. In: Handbook of Physiology. Respiration Vol. I. Washington D.C.: Am. Physiol. Soc. 1964.
Roughton, F. J. W.: Some recent work on the interactions of oxygen, carbon dioxide and haemoglobin. Biochem. J. 117, 801–812 (1970).
Roughton, F. J. W., Deland, E. C., Kernohan, J. C., Severinghaus, J. W.: Some recent studies of the oxyhaemoglobin dissociation curve of human blood under physiological conditions and the fitting of the Adair equation to the standard curve. In: Oxygen affinity of hemoglobin and red cell acid base status. Copenhagen: Munksgaard, 1972.
Roughton, F. J. W., Otis, A. B., Lyster, R. L. J.: The determination of the individual equilibrium constants of the four intermediate reactions between oxygen and sheep haemoglobin. Proc. R. Soc. Lond. (Biol.) 144, 29–54 (1955).
Salhany, J. M., Mathers, D. H., Eliot, R. S.: The deoxygenation kinetics of hemoglobin partially saturated with carbon monoxide. J. biol. Chem. 247, 6985–6990 (1972).
Saltin, B., Gagge, A. P., Stolwijk, J. A. J.: Muscle temperature during submaximal exercise in man. J. appl. Physiol. 25, 679–688 (1968).
Shulman, R. G., Ogawa, S., Hopfield, J. J.: An allosteric model of hemoglobin. Arch. Biochem. Biophys. 151, 68–74 (1972).
Sick, H., Gersonde, K., Thompson, J. C., Maurer, W., Haar, W., Rüterjans, H.: The Bohr proton binding site in a monomeric haemoglobin. Eur. J. Biochem. 29, 217–223 (1972).
Siegfried, M.: Über die Bindung von Kohlensäure durch amphotere Amidokörper. Z. Phys. Chem. 44, 85–96 (1905).
Siggaard-Andersen, O.: Oxygen-linked hydrogen binding of human hemoglobin. Effects of carbon dioxide and 2,3-diphosphoglycerate. I. Studies on erythrolysate. Scand. J. clin. Lab. Invest. 27, 351–360 (1971).
Siggaard-Andersen, O., Salling, N.: Oxygen-linked hydrogen binding of human hemoglobin. Effects of carbon dioxide and 2,3-diphosphoglycerate. II. Studies on whole blood. Scand. J. clin. Lab. Invest. 27, 361–366 (1971).
Siggaard-Andersen, O., Salling, N., Nörgaard, B., Rørth, M.: Oxygen-linked hydrogen binding of human hemoglobin. Effects of carbon dioxide and 2,3-diphosphoglycerate. III. Comparison of the Bohr effect and the Haldane effect. Scand. J. clin. Lab. Invest. 29, 185–193 (1972).
Schroeder, W. A.: The hemoglobins. Ann. Rev. Biochem. 32, 301–320 (1963).
Schroeder, W. A., Jones, R. T.: Some aspects of the chemistry and function of human and animal hemoglobins. Fortschr. Chem. Org. Naturst. 23, 113–194 (1965).
Slyke van, D. D., Hastings, A. B., Murray, C. D., Sendroy, J.: Studies of gas and electrolyte equilibria in blood. VIII. The distribution of hydrogen, chloride and bicarbonate ions in oxygenated and reduced blood. J. biol. Chem. 65, 701–728 (1925).
Stadie, W. C., O'Brien, H.: The carbamate equilibrium. II. The equilibrium of oxyhemoglobin and reduced hemoglobin. J. biol. Chem. 117, 439–470 (1937).
Thorling, E. B., Erslev, A. J.: The “tissue” tension of oxygen and erythropoiesis. Blood 31, 332–343 (1968).
Tomita, S., Riggs, A.: Studies on the interaction of 2,3-diphosphoglycerate and carbon dioxide with hemoglobins from mouse, man and elephant. J. biol. Chem. 246, 547–554 (1971).
Tyuma, I., Shimizu, K.: Different response to organic phosphates of human fetal and adult hemoglobins. Arch. Biochem. Biophys. 129, 404–405 (1969).
Tyuma, I., Shimizu, K., Imai, K.: Effect of 2,3-diphosphoglycerate on the cooperativity in oxygen binding of human adult hemoglobin. Biochem. Biophys. Res. Commun. 43, 423–428 (1971).
Valeri, C. R., Fortier, N. L.: Red cell 2,3-diphosphoglycerate and creatine levels in patients with red cell mass deficits or with cardio-pulmonary insufficiency. N. Engl. J. Med. 281, 1452–1455 (1969).
Valeri, C. R., Zaroulis, C. G., Fortier, N. L.: Peripheral red cells as a functional biopsy to determine tissue oxygen tension. In: Oxygen affinity of hemoglobin and red cell acid base status. Copenhagen: Munksgaard 1972.
Varnauskas, E., Björntorp, P., Fahlen, M., Prerovsky, I., Stenberg, J.: Effects of physical training on exercise blood flow and enzymatic activity in skeletal muscle. Cardiovasc. Res. 4, 418–422 (1970).
Verdier de, C. H., Garby, L.: Low binding of 2,3-diphosphoglycerate to haemoglobin F. A contribution to the knowledge of the binding site and an explanation for the high oxygen affinity of foetal blood. Scand. J. clin. Lab. Invest. 23, 149–151 (1969).
Versmold, H., Brauser, B.: Improved cellular oxygenation by 2,3-diphosphoglycerate: Quantitative measurement of tissue hypoxia by registration of absorption spectra of cytochrome a and hemoglobin in the intact organ. In: Erythrocytes, Thrombocytes, Leucocytes. Stuttgart: Thieme 1973.
Versmold, H., Wenner, J., Riegel, K.: Changes of blood oxygen affinity and capacity and red cell 2,3 DPG evoked by exchange transfusions with ACD preserved blood in newborn infants: their interrelationship and influences on oxygen supply of tissues and erythropoiesis. Z. Kinderheilk. 113, 1–18 (1972).
Viale, R. O., Maggiora, G. M., Ingraham, L. M.: Molecular orbital evidence for Weiss's oxyhaemoglobin structure. Nature (Lond.) 203, 183–184 (1964).
Wang, J. H.: Hemoglobin studies. II. A synthetic material with hemoglobin-like property. J. Am. Chem. Soc. 80, 3168–3169 (1958).
Wang, J. H., Nakahara, A., Fleischer, E. B.: Hemoglobin studies. I. The combination of carbon monoxide with hemoglobin and related model compounds. J. Am. Chem. Soc. 80, 1109–1113 (1958).
Weber, G.: Ligand binding and internal equilibria in proteins. Biochemistry 11, 864–878 (1972).
Weiss, J. J.: Nature of the iron-oxygen bond in oxyhaemoglobin. Nature (Lond.) 202, 83–84 (1964).
Whitehaed, E.: The regulation of enzyme activity and allosteric transition. Progr. Biophys. Mol. Biol. 21, 321–397 (1970).
Wittenberg, J. B., Wittenberg, B. A., Peisach, J., Blumberg, W. E.: On the state of the iron and the nature of the ligand in oxyhaemoglobin. Proc. nat. Acad. Sci. (Wash.) 67, 1846–1853 (1970).
Woodson, R. D., Torrance, J. D., Shappell, S. D., Lenfant, C.: The effect of cardiac disease on hemoglobin oxygen binding. J. clin. Invest. 49, 1349–1356 (1970).
Wranne, B., Woodson, R. D., Detter, J. C.: Bohr effect: interaction between H+, CO2, and 2,3-DPG in fresh and stored blood. J. appl. Physiol. 32, 749–754 (1972).
Wyman, J.: Heme proteins. Adv. Protein Chem. 4, 407–531 (1948).
Wyman, J.: Allosteric effects in hemoglobin. Cold Spring Harbor Symp. Quant. Biol. 28, 483–489 (1963).
Wyman, J.: Allosteric linkage. J. Am. Chem. Soc. 89, 2202–2218 (1967).
Wyman, J., Allen, D. W.: The problem of the heme interactions in hemoglobin and the basis of the Bohr effect. J. Polym. Sci. 7, 499–518 (1951).
Zuckerkandl, E., Pauling, L.: Molecular disease, evolution and genetic heterogeneity. In: Horizons in Biochemistry. New York-London: Academic Press 1962.
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Bauer, C. (1974). On the respiratory function of haemoglobin. In: Reviews of Physiology, Biochemistry and Pharmacology, Volume 70. Reviews of Physiology, Biochemistry and Pharmacology, vol 70. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0034292
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