Facilitated Diffusion of Oxygen: Possible Significance in Blood and Muscle

  • F. Kreuzer
  • L. Hoofd
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 169)


Facilitated diffusion of a permeant is transport with a rate faster than that according to the diffusive conditions of the permeant. This enhancement may be effected by a molecular carrier reversibly reacting with the permeant. The kind of facilitated transport where the permeant is transported both in free form and combined with a carrier (as pertains to oxygen) is called “carrier-mediated transport” (Schultz et al., 1974). Such a carrier shows saturation behavior due to the finite concentration of carrier and can be inhibited by molecules structurally similar to and thus competing with the carried species. The total transport is the sum of the two components, free diffusion and the permeant and the diffusion of the carrier loaded with the permeant. These two movements obey their respective concentration gradients which are not independent but related by the rates of chemical reactions between permeant and carrier. Carrier-mediated transport therefore belongs to the class of reaction-enhanced transport and is analyzed as a problem of diffusion coupled with reversible chemical reactions. After the establishment of facilitation of O2 diffusion in the presence of hemoglobin or myoglobin by Klug et al. (1956), Wittenberg (1959) and Scholander (1960), much experimental and theoretical work during the past two decades has clarified the mechanism and the conditions of this phenomenon.


Oxygen Transport Oxygen Carrier Permeability Ratio Damkohler Number Hemoglobin Solution 
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  1. Bârzu, O., and Satre, M., 1970, Determination of oxygen affinity of respiratory systems using oxyhemoglobin as oxygen donor, Anal. Biochem., 36: 428–433.PubMedCrossRefGoogle Scholar
  2. Buerk, D.G., and Longmuir, I.S., 1977, Evidence for nonclassical respiratory activity from oxygen gradient measurements in tissue slices, Microvasc. Res., 13: 345–353.PubMedCrossRefGoogle Scholar
  3. Buerk, D.G., and Saidel, G.M., 1978, A comparison of two nonclassical models for oxygen consumption in brain and liver tissue, in.: “Oxygen Transport to Tissue — III”, I.A. Silver, M. Erecińska, H.I. Bicher, eds., Adv. Exper. Med. Biol., Vol. 94, Plenum Press, New York — London, pp. 225–232.CrossRefGoogle Scholar
  4. Burns, B., and Gurtner, G.H., 1973, A specific carrier for oxygen and carbon monoxide in the lung and placenta, Drug Metab. Dispos., 1: 374–379.PubMedGoogle Scholar
  5. Burns, B., and Shephard, R.H., 1981, Membrane diffusion: Comparison between dithionite DO2 and DLCO, in: “Progress in Respiration Research”, Vol. 16, J. Piiper, P. Scheid, eds., Karger, BaselMünchen-Paris-London-New York-Sidney, pp. 130–141.Google Scholar
  6. Chance, B., 1965, Reaction of oxygen with the respiratory chain in cells and tissues, J. Gen. Physiol., 49: 163–188.PubMedCrossRefGoogle Scholar
  7. Cole, R.P., 1982, Myoglobin function in exercising skeletal muscle, Science, 216: 523–525.PubMedCrossRefGoogle Scholar
  8. Cole, R.P., Wittenberg, B.A., and Caldwell, P.R.B., 1978, Myoglobin function in the isolated fluorocarbon-perfused dog heart, Am. J. Physiol., 234: H567–H572.PubMedGoogle Scholar
  9. Diller, T.E., and Mikic, B.B., 1980, Modeling the oxygen diffusion effects of red cell motions in flowing blood, in.: “Advances in Bioengineering”, C.V. Mow, ed., Am. Soc. Mech. Eng., New York, pp. 177–180.Google Scholar
  10. Engasser, J.M., 1978, A fast evaluation of diffusion effects on bound enzyme activity, Biochim. Biophys. Acta, 526: 301–310.PubMedCrossRefGoogle Scholar
  11. Fletcher, J.E., 1980, On facilitated diffusion in muscle tissues, Biophys. J., 29: 437–458.PubMedCrossRefGoogle Scholar
  12. Friedlander, S.K., and Keller, K.H., 1965, Mass transfer in reacting systems near equilibrium. Use of the affinity function, Chem. Eng. Sci., 20: 121–129.CrossRefGoogle Scholar
  13. Gayeski, T.E.J., and Honig, C.R., 1978, Myoglobin saturation and calculated Po2 in single cells of resting gracilis muscle, in.: “Oxygen Transport to Tissue — III”, I.A. Silver, M. Erecinska, H.I. Bicher, eds., Adv. Exper. Med. Biol., Vol. 94, Plenum Press, New York — London, pp. 77–84.CrossRefGoogle Scholar
  14. Gijsbers, G.H., and van Ouwerkerk, H.J., 1976, Boundary layer resistance of steady-state oxygen diffusion facilitated by a four-step chemical reaction with hemoglobin in solution, Pflügers Arch., 365: 231–241.PubMedCrossRefGoogle Scholar
  15. Goddard, J.D., 1977, Further applications of carrier-mediated transport theory — a survey, Chem. Eng. Sci., 32: 795–809.CrossRefGoogle Scholar
  16. Goddard, J.D., Schultz, J.S., and Bassett, R.J., 1970, On membrane diffusion with near-equilibrium reaction, Chem. Eng. Sci., 25: 665–683.CrossRefGoogle Scholar
  17. Gonzales-Fernandez, J.M., and Atta, S.E., 1981, Transport of oxygen in solutions of hemoglobin and myoglobin, Math. Biosci., 54: 265–290.CrossRefGoogle Scholar
  18. Gonzales-Fernandez, J.M., and Atta, S.E., 1982, Facilitated transport of oxygen in the presence of membranes in the diffusion path, Biophys. J., 38: 133–141.CrossRefGoogle Scholar
  19. Gurtner, G.H., and Burns, B., 1972, Possible facilitated transport of oxygen across the placenta, Nature, 240: 473–475.PubMedCrossRefGoogle Scholar
  20. Gurtner, G.H., and Peavy, H.H., 1981, Evidence for facilitated transport of O2 and CO in the lungs, in.: “Progress in Respiration Research”, Vol. 16, J. Piiper, P. Scheid, eds., Karger, Basel-München-Paris-London-New York-Sidney, pp. 161–165.Google Scholar
  21. Gurtner, G.H., Traystman, R.J., and Burns, B., 1982, Interactions between placental O2 and CO transfer. J. Appl. Physiol.:Respirat. Environ. Exercise Physiol., 52: 479–487.Google Scholar
  22. Hoofd, L., and Kreuzer, F., 1979, A new mathematical approach for solving carrier-facilitated steady-state diffusion problems, J. Math. Biol., 8: 1–13.PubMedCrossRefGoogle Scholar
  23. Jones, D.P., and Mason, H.S., 1978, Gradients of O2 concentration in hepatocytes, J. Biol. Chem., 253: 4874–4880.PubMedGoogle Scholar
  24. Jones, H.A., Buckingham, P.D., Clark, J.C., Forster, R.E., Heather, J.D., Hughes, J.M.B., and Rhodes, C.G., 1981, Constant rate of CO uptake with variable inspired CO concentration, in.: “Progress in Respiration Research”, Vol. 16, J. Piiper, P. Scheid, eds., Karger, Basel-München-Paris-London-New York-Sidney, pp. 69–171.Google Scholar
  25. Kawashiro, T., Piiper, J., and Scheid, P., 1978, Dependence of O2 uptake on surface Po2 in intact, excised skeletal muscle of the rat: validity of the Warburg model, J. Physiol., 284: 45P–46P.PubMedGoogle Scholar
  26. Klug, A., Kreuzer, F., and Roughton, F.J.W., 1956, The diffusion of oxygen in concentrated hemoglobin solutions, Helv. Physiol. Pharm. Acta, 14: 121–128.Google Scholar
  27. Knoblauch, A., Sybert, A., Brennan, N.L., Sylvester, J.T., and Gurtner, G.H., 1981, Effect of hypoxia and CO on a cytochrome P-450-mediated reaction in rabbit lungs, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 51: 1635–1642.Google Scholar
  28. Koning, de, J., Hoofd, L.J.C., and Kreuzer, F., 1981, Oxygen transport and the function of myoglobin. Theoretical model and experiments in chicken gizzard smooth muscle, Pflügers Arch., 389: 211–217.PubMedCrossRefGoogle Scholar
  29. Kreuzer, F., 1970, Facilitated diffusion of oxygen and its possible significance; a review, Respir. Physiol., 9: 1–30.PubMedCrossRefGoogle Scholar
  30. Kreuzer, F., and Hoofd, L.J.C., 1970, Facilitated diffusion of oxygen in the presence of hemoglobin, Respir. Physiol., 8: 280–302.PubMedCrossRefGoogle Scholar
  31. Kreuzer, F., and Hoofd, L.J.C., 1972, Factors influencing facilitated diffusion of oxygen in the presence of hemoglobin and myoglobin, Respir. Physiol., 15: 104–124.PubMedCrossRefGoogle Scholar
  32. Kreuzer, F., and Hoofd, L., 1982, Facilitated diffusion of O2 and CO2, in “Handbook of Physiology: Respiration”, L.E. Farhi, S.M. Tenney, eds., American Physiological Society, Bethesda, Md., in press.Google Scholar
  33. Kreuzer, F., and Yahr, W.Z., 1960, Influence of red cell membrane on diffusion of oxygen, J. Appl. Physiol., 15: 1117–1122.PubMedGoogle Scholar
  34. Kutchai, H., 1970, Numerical study of oxygen uptake by layers of hemoglobin solution, Respir. Physiol., 10: 273–284.PubMedCrossRefGoogle Scholar
  35. Kutchai, H., 1971, O2 uptake by 100 u layers of hemoglobin solution, Respir. Physiol., 11: 378–383.PubMedCrossRefGoogle Scholar
  36. Kutchai, H., Jacquez, J.A., and Mather, F.J., 1970, Nonequilibrium facilitated oxygen transport in hemoglobin solution, Biophys. J., 10: 38–54.PubMedCrossRefGoogle Scholar
  37. Longmuir, I.S., and McCabe, M.G.P., 1964, Evidence for an oxygen carrier in tissue, J. Polarogr. Soc, 10: 45–48.Google Scholar
  38. Longo, L.D., 1978, Placental diffusing capacity for carobon monoxide. Letter to the Editor, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 45: 155.Google Scholar
  39. Meyer, M., Lessner, W., Scheid, P., and Piiper, J., 1981, Pulmonary diffusing capacity for CO independent of alveolar CO concentration, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 51: 571–576.Google Scholar
  40. Mitchell, P.J., and Murray, J.D., 1973, Facilitated diffusion: The problem of boundary conditions, Biophysik, 9: 177–190.PubMedCrossRefGoogle Scholar
  41. Müller, J., and Zwing, T., 1982, An experimental verification of the theory of diffusion limitation of immobilized enzymes, Biochim. Biophys. Acta, 705: 117.123.PubMedCrossRefGoogle Scholar
  42. Oshino, R., Oshino, N., Tamura, M., Kobilinsky, L., and Chance, B., 1972, A sensitive bacterial luminiscence probe for O2 in biochemical systems, Biochim. Biophys. Acta, 273: 5–17.PubMedCrossRefGoogle Scholar
  43. Rubin, D.Z., Fujino, D., Mittman, C, and Lewis, S.M., 1981, Competitive inhibition of carbon monoxide transport: evidence against a carrier, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 50: 1061–1064.Google Scholar
  44. Scholander, P.F., 1960, Oxygen transport through hemoglobin solutions, Science, 131: 585–590.PubMedCrossRefGoogle Scholar
  45. Schultz, J.S., Goddard, J.D., and Suchdeo, S.R., 1974, Facilitated transport via carrier-mediated diffusion in membranes. Part I. Mechanistic aspects, experimental systems and characteristic regimes, AIChE J., 20: 417–445.CrossRefGoogle Scholar
  46. Schwarzmann, V., and Grunewald, W.A., 1978, Myoglobin-O2-saturation profiles in muscle sections of chicken gizzard and the facilitated O2-transport by Mb, in.: “Oxygen Transport to Tissue — III”, I.A. Silver, M. Erecińska, H.I. Bicher, eds., Adv. Exper. Med. Biol., Vol. 94, Plenum Press, New York — London, pp. 301–310.CrossRefGoogle Scholar
  47. Smith, K.A., Meldon, J.H., and Colton, C.K., 1973, An analysis of carrier-facilitated transport, AIChE J., 19: 102–111.CrossRefGoogle Scholar
  48. Starlinger, H., and Lübbers, D.W., 1973, Polarographic measurements of the oxygen pressure performed simultaneously with optical measurements of the redox state of the respiratory chain in suspensions of mitochondria under steady-state conditions at low oxygen tensions, Pflügers Arch., 341: 15–22.PubMedCrossRefGoogle Scholar
  49. Stroeve, P., Colton, C.K., and Smith, K.A., 1976, Steady state diffusion of oxygen in red blood cell and model suspensions, AIChE J., 22: 1133–1142.CrossRefGoogle Scholar
  50. Stroeve, P., and Eagle, K., 1980, Myoglobin-facilitated oxygen transport in heterogeneous red muscle tissue, in.: “Advances in Bioengineering”, C.V. Mow, ed., Am. Soc. Mech. Eng., New York, pp. 341–344.Google Scholar
  51. Tamura, M. Oshino, N., Chance, B., and Silver, I.A., 1978, Optical measurements of intracellular oxygen concentration of rat heart in vitro, Arch. Biochem. Biophys., 191: 8–22.PubMedCrossRefGoogle Scholar
  52. Weigelt, H., 1975, Mikrophotometrische Messungen zur Untersuchung des erleichterten Sauerstofftransports in Gegenwart von Hämoglobin, Dissertation, Ruhr-Universität Bochum.Google Scholar
  53. Wilson, D.F., Erecińska, M., Brown, S., and Silver, I.A., 1979, The oxygen dependence of cellular energy metabolism, Arch. Biochem. Biophys., 195: 485–493.PubMedCrossRefGoogle Scholar
  54. Wittenberg, J.B., 1959, Oxygen transport — a new function proposed for myoglobin, Biol. Bull., 117: 402–403.Google Scholar
  55. Wittenberg, J.B., 1970, Myoglobin-facilitated oxygen diffusion: Role of myoglobin in oxygen entry into muscle, Physiol. Rev., 50: 559–636.PubMedGoogle Scholar
  56. Wittenberg, B.A., Wittenberg, J.B., and Caldwell, P.R.B., 1975, Role of myoglobin in the oxygen supply to red skeletal muscle, J. Biol. Chem., 250: 9038–9043.PubMedGoogle Scholar
  57. Wittenberg, J.B., and Wittenberg, B.A., 1981, Facilitated oxygen diffusion by oxygen carriers, in.: “Oxygen and Living Processes”, D.L. Gilbert, ed., Springer, New York.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • F. Kreuzer
    • 1
  • L. Hoofd
    • 1
  1. 1.Department of PhysiologyUniversity of NijmegenNijmegenThe Netherlands

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