Hemoglobin Oxygen Binding, Erythrocyte Shape Transformations, and Modeling of Cell Differentiation as Examples of Theoretical Approaches in Studying the Structure-Function Relationship in Biological Systems

  • Saša Svetina


Any attempt to express functional behavior of a biological system in terms of the physical and chemical properties of its constituents must involve relating together different levels of complexity of a system’s structure. At different levels of the system, the structures are described by different observable quantities determinable by different experimental approaches. The understanding of the macroscopic behavior of a certain structure, including its function, on the basis of its microscopic properties can be in many instances achieved simply by correlating the observations obtained at different levels of study. However, in many other instances such an understanding is possible only on the basis of quantitative relationships which are the result of an appropriate theory. Theoretical approaches in biology play the same role as theoretical approaches in physics and chemistry, such as statistical mechanics where the thermodynamic properties of the system are determined on the basis of properties of atoms and molecules and their interactions, or quantum chemistry where properties of atoms and molecules are determined from interactions between the constituents of the atom. Biological systems comprise a large number of different levels of organization, from atoms and molecules to macromolecules, solutions, supramolecular structures, cells, cell populations, tissues, organs, organisms, etc. Relating system properties at two such levels must take into consideration specific features in the description of a system at a given level and it is expected that the corresponding theory reflects these features. Therefore many different theoretical approaches need to be developed in order to cover all possible relationships. These lectures are aimed at giving an example of three different theoretical approaches, each relating a different pair of levels of structural complexity in biological system. The relations between the macrómolecular structure and the thermodynamic behavior of the system of a macromolecule and its ligands will be dealt with in the lecture on the relationship between hemoglobin structure and its ligand binding behavior. Relationship between the cell shape and the properties of the cell membrane will be discussed in the lecture on interaction of charged membranes with surrounding ions and ion induced shape and volume changes of red blood cell ghosts. The properties of the cell population will be related to the properties of a chemical system at the level of a single cell in the lecture on modeling the molecular basis of cell differentiation. Although the topics discussed in these lectures are all connected with the system of oxygen delivery in vertebrate organisms, they represent rather different aspects of this system and therefore the material is organized in such a way that each lecture is contained in a separate chapter. Chapters are independent and selfsufficient as regards the nomenclature. References are also listed separately for each chapter.


Stable Steady State Oxygen Binding Hemoglobin Molecule Electrostatic Free Energy Murine Erythroleukemia Cell 
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Chapter 1

  1. Adair, G., 1925, The haemoglobin system. VI. The oxygen dissociation curve of haemoglobin, J. Biol. Chem., 63:529.Google Scholar
  2. Antonini, E., and Brunori, M., 1971, “Hemoglobin and Myoglobin in Their Reactions with Ligands”, North Holland, Amsterdam.Google Scholar
  3. Arnone, A., 1972, X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhemoglobin, Nature, 237:146.ADSCrossRefGoogle Scholar
  4. Asakura, T., and Lau, P.-W., 1978, Sequence of oxygen binding by hemoglobin, Proc. Natl. Acad. Sci. USA, 75:5462.ADSCrossRefGoogle Scholar
  5. Baldwin, J.M., 1975, Structure and function of hemoglobin, Progr. Biophys. Mol. Biol., 29:225.CrossRefGoogle Scholar
  6. Benesch, R.E., and Benesch, R., 1974, The mechanism of interaction of red cell organic phosphates with hemoglobin, Adv. Protein Chem., 28:211.CrossRefGoogle Scholar
  7. Coleman, P.F., 1977, A study of conformational changes in two β-93 modified hemoglobin A’s using a triphosphate spin label, Biochemistry, 16:345.CrossRefGoogle Scholar
  8. Herzfeld, J., and Stanley, H.E., 1974, A general approach to cooperativity and its application to the oxygen equilibrium of haemoglobin and its effectors, J. Mol. Biol., 82:231.CrossRefGoogle Scholar
  9. Imai, K., and Yonetani, T., 1975, pH dependence of the Adair constants of human hemoglobin, J. Biol. Chem., 250:2227.Google Scholar
  10. Imaizumi, K., Imai, K., and Tyuma, I., 1979, The linkage between the four-step binding of oxygen and the binding of heterotropic anionic ligands in hemoglobin, J. Biochem., 86:1829.Google Scholar
  11. Karabeg-Musemić, R., and Svetina, S., 1979, On the relationship between oxygen binding to normal and specifically modified hemoglobins, abstract S7–50, in: “FEBS Special Meeting on Enzymes”, Dubrovnik-Cavtat.Google Scholar
  12. Kilmartin, J.V., and Rossi-Bernardi, L., 1973, Interaction of hemoglobin with hydrogen ions, carbon-dioxide, and organic phosphates, Physiol. Rev., 53:836.Google Scholar
  13. Koshland, D.E., Jr., Nemethy, G., and Filmer, D., 1966, Comparison of experimental binding data and theoretical models in proteins containing subunits, Biochemistry, 5:365.CrossRefGoogle Scholar
  14. Monod, J., Wyman, J., and Changeux, J.-P., 1965, On the nature of allosteric transitions: a plausible model, J. Mol. Biol., 12:88.CrossRefGoogle Scholar
  15. Ogata, R.T., and McConnell, H.M., 1972, States of hemoglobin in solution, Biochemistry, 11:4792.CrossRefGoogle Scholar
  16. Pauling, L., 1935, The oxygen equilibrium of hemoglobin and its structural interpretation, Proc. Natl. Acad. Sci. USA, 21:186.ADSCrossRefGoogle Scholar
  17. Perutz, M.F., 1970, Stereochemistry of cooperative effects in hemoglobin, Nature, 228:726.ADSCrossRefGoogle Scholar
  18. Perutz, M.F., 1976, Structure and mechanism of haemoglobin, Br. Med. Bull., 32:195.Google Scholar
  19. Perutz, M.F., Kilmartin, J.V., Nishikura, K., Fogg, J.H., Butler, P.J.G., and Rollema, H.S., 1980, Identification of residues contributing to the Bohr effect of human haemoglobin, J. Mol. Biol., 138:649.CrossRefGoogle Scholar
  20. Šmigoc, K., 1981, Generalized Adair-equation for binding of oxygen, hydrogen ions and 2,3-diphosphoglycerate to normal human hemoglobin, Mag. Thesis, University of Zagreb, in Slovene.Google Scholar
  21. Svetina, S., 1971., Thermodynamic studies of mechanisms for cooperativity in proteins containing subunits, in: “Proc. First European Biophysics Congress”, E. Broda, A. Locker and H. Springer-Lederer, eds., Verlag der Wiener Medizinischen Akademie, Vienna, p. 85.Google Scholar
  22. Svetina, S., 1973, Thermodynamical studies of cooperative oxygen binding by hemoglobin, in: “Proc. VII. Internationales Symposium über Strukture und Funktion der Erytrozyten”, Anhandlungen der Akademie der Wissenschaften der DDR, Berlin, p. 135.Google Scholar
  23. Szabo, A., and Karplus, M., 1972, Mathematical model for structure-function relations in haemoglobin, J. Mol. Biol., 72:163.CrossRefGoogle Scholar
  24. Wyman, J., 1972, On allosteric models, in: “Current Topics in Cellular Regulation”, Academic Press, Inc., New York and London, p. 209.Google Scholar

Chapter 2

  1. Evans, E.A., and Hochmuth, R.M., 1978, Mechanochemical properties of membranes, Curr. Top. Membr. Transp., 10:1.CrossRefGoogle Scholar
  2. Jähnig, F., 1976, Electrostatic free energy and shift of the phase transition for charged lipid membranes, Biophys. Chem., 4:309.CrossRefGoogle Scholar
  3. Johnson, R.M., Taylor, G., and Meyer, D.B., 1980, Shape and volume changes in erythrocyte ghosts and spectrin-acting networks, J. Cell. Biol., 86:371.CrossRefGoogle Scholar
  4. McLaughlin, S., 1976, Electrostatic potentials at membrane-solution interfaces, Curr. Top. Membr. Transp., 9:71.CrossRefGoogle Scholar
  5. Sheetz, M.P., and Singer, S.J., 1974, Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions, Proc. Natl. Acad. Sci. USA, 71:4457.ADSCrossRefGoogle Scholar
  6. Svetina, S., Ottova-Leitmannova, A., and Glaser, R., 1982, Membrane bending energy in relation to bilayer couples concept of red blood cell shape transformations, J. Theor. Biol., 94:13.CrossRefGoogle Scholar
  7. Verkleij, A.J., Zwaal, R.F.A., Roelofsen, B., Comfurius, P., Kastelijn, D., and Van Deenen, L.L.M., 1973, The asymmetric distribution of phospholipids in the human red blood cell membrane, Biochim. Biophys. Acta, 323:178.CrossRefGoogle Scholar

Chapter 3

  1. Berg, O.G., and Blomberg, C., 1977, Mass action relations in vivo with application to the 1ac operon, J. Theor. Biol., 67:523.CrossRefGoogle Scholar
  2. Edelstein, B.B., 1972, The dynamics of cellular differentiation and associated pattern formation, J. Theor. Biol., 37:221.CrossRefGoogle Scholar
  3. Griffith, J.S., 1968, Mathematics of cellular control processes II. Positive feedback to one gene, J. Theor. Biol., 20:209.CrossRefGoogle Scholar
  4. Housman, D., Gusella, J., Geller, R., Levenson, R., and Weil, S., 1978, Differentiation of murine erythroleukemia cells: The central role of the commitment event, in: “Cold Spring Harbor Conferences on Cell Proliferation. Vol. 5. Differentiation of Normal and Neoplastic Hematopoietic Cells”, B. Clarkson, P.A. Marks, and J.E. Till, eds., Cold Spring Harbor Press, Cold Spring Harbor, N.Y., p. 193.Google Scholar
  5. Levenson, R., and Housman, D., 1979, Developmental program of murine erythroleukemia cells. Effect of the inhibition of protein synthesis, J. Cell. Biol., 82:715.CrossRefGoogle Scholar
  6. Levenson, R., Kernen, J., and Housman, D., 1979, Synchronization of MEL cell commitment with cordycepin, Cell, 18:1073.CrossRefGoogle Scholar
  7. Lewis, J., Slack, J.M.W., and Wolpert, L., 1977, Thresholds in development, J. Theor. Biol., 65:579.CrossRefGoogle Scholar
  8. Marks, P.A., and Rifkind, R.A., 1978, Erythroleukemic differentiation, Ann. Rev. Biochem., 47:419.CrossRefGoogle Scholar
  9. Meinhardt, H., and Gierer, A., 1980, Generation and regeneration of sequence of structures during morphogenesis, J. Theor. Biol. 85:429.MathSciNetCrossRefGoogle Scholar
  10. Monod, J., and Jacob, F., 1961, General conclusions: Teleonomic mechanisms in cellular metabolism, growth, and differentiation, Cold Spring Harbor Symposia on Quantitative Biology, 26:389.CrossRefGoogle Scholar
  11. Svetina, S., 1981, Protein induction process and stochastic nature of cell commitment to proliferation and differentiation, J. Theor. Biol., 90:151.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Saša Svetina
    • 1
  1. 1.Institute of Biophysics Medical Faculty and “J. Stefan” InstituteE. Kardelj UniversityLjubljanaYugoslavia

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