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Carbon Dioxide Transport

Robert A. Klocke

10.1002/cphy.cp030410

Source: Supplement 13: Handbook of Physiology, The Respiratory System, Gas Exchange

Originally published: 1987

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Carbon Dioxide Content of Blood
1.1 Dissolved CO2
1.2 Bicarbonate Ion
1.3 Carbamate Compounds
2 Carbon Dioxide Dissociation Curve
2.1 Buffering of CO2
2.2 Distribution of CO2 Content Between Cells and Plasma
2.3 Haldane Effect
2.4 Relative Contributions to CO2 Exchange
3 Time‐Dependent Factors in CO2 Exchange
3.1 Diffusion of CO2
3.2 Dehydration of Carbonic Acid
3.3 Bicarbonate‐Chloride Exchange
3.4 Interaction of CO2 and O2 Exchange
3.5 Models of Gas Exchange
Figure 1. Figure 1.

Pathways for hydration‐dehydration reaction. The k2–k′2 reaction is much faster than other two reactions, which are rate limiting for the process.
Figure 2. Figure 2.

Arrhenius plot illustrating effect of temperature on constants involved in CO2 reactions. Straight lines fitted to experimental data are given by Constant (log10) = m [103/T(°K)] + b; m and b values for each process are listed in figure.

Data for feoir from Pinsent et al. 118 and Sirs 138. Data for from Edsall 38. Data for from Roughton 129. Hydration constant Kh computed from and
Figure 3. Figure 3.

Effect of pH on Michaelis constant (Km; A) and turnover number (kcat; B) of human carbonic anhydrase I (HCA‐B) and II (HCA‐C) at 25°C and 0.2 M ionic strength. The pH variation of kcat/Km is result of changes in kcat because Km is constant over this pH range. The following buffers were used in the experiments: ▿, 3,5‐lutidine; ○, imidazole; □, N‐methylimidazole; Δ, 1,2‐dimethylimidazole.

From Khalifah 81
Figure 4. Figure 4.

Oscilloscopic tracing of change in pH after rapid mixing (STOP) of solution containing CO2 with 4 mM glycylglycine at 37°C. pHA, pH of glycylglycine solution prior to mixing. pHB, pH of mixture after mixing but prior to reaction. pHequil, carbamate equilibrium; subsequent pH change is due to continuing uncatalyzed hydration of CO2. pHc, extrapolation of pH to time of mixing; this pH would occur as result of carbamate formation alone.

From Gros et al. 60
Figure 5. Figure 5.

Carbamate dissociation curves of human plasma at 37°C.

From Gros et al. 60
Figure 6. Figure 6.

Carbon dioxide content of deoxygenated solutions of human Hb at constant partial pressure of CO2 (Pco2, 40 Torr). Upper curve obtained in absence of 2,3‐DPG; lower curve obtained after addition of 2 mol 2,3‐DPG/mol Hb tetramer.

From Bauer 10
Figure 7. Figure 7.

Influence of 2,3‐diphosphoglycerate (2,3‐DPG) on Haldane effect in erythrocytes. •, Data obtained with carbonic anhydrase inhibition, ▴, Data obtained without carbonic anhydrase inhibition. Relative contributions of (clear areas) and carbamate (shaded areas) to total Haldane effect are labeled.

Adapted from Klocke 86
Figure 8. Figure 8.

Carbon dioxide bound to β‐chain (A) and α‐chain (B) of Hb selectively carbamylated at NH2‐terminal amino groups. ○, □, Deoxygenated solutions. •, ▪, Solutions of Hb liganded with CO. ○, •, Solutions free of 2,3‐DPG. □, ▪, Data obtained in presence of 2 mol 2,3‐DPG/mol Hb tetramer.

From Perrella et al. 111. Reprinted by permission from Nature, copyright 1975, MacMillan Journals Limited
Figure 9. Figure 9.

Carbon dioxide dissociation curve of human blood plotted on linear (A) and logarithmic (B) axes.

Data from Christiansen et al. 27
Figure 10. Figure 10.

Reactions of CO2 in pulmonary capillary. CA, carbonic anhydrase, either free inside cell or bound to capillary endothelium. ‐ ‐>, Dehydration reaction proceeds much more slowly in plasma than erythrocyte. →, Processes that proceed rapidly. ‐‐‐>, Participation of H+ associated with Hb buffering.
Figure 11. Figure 11.

Variation in Haldane effect as function of extracellular pH at Pco2 of 42.5 Torr in erythrocyte suspensions. •, Data obtained with carbonic anhydrase inhibition. x, Data obtained without carbonic anhydrase inhibition. Contributions of oxylabile carbamate and to total Haldane effect are indicated.

From Klocke 86
Figure 12. Figure 12.

Carbon dioxide excretion () in isolated, blood‐free perfused rabbit lungs as function of perfusion rate (). ▴, Observed CO2 excretion. Δ, Expected excretion of CO2 dissolved in buffer, calculated from simultaneous measurements of excretion of acetylene dissolved in buffer. Shaded areas, CO2 generated in pulmonary capillary from contained in perfusate. Small amount of CO2 generated in presence of acetazolamide (B) is result of uncatalyzed dehydration reaction. Larger amount formed under control conditions (A) is due to catalysis of dehydration by capillary endothelial carbonic anhydrase.

From Klocke 89
Figure 13. Figure 13.

Lineweaver‐Burk plot of reciprocals of reaction velocity (V) and substrate () concentration in presence of different concentrations of acetazolamide (ACTZ). •, 12 mM in perfusate; ○, 25 mM in perfusate; ▴, 35 mM in perfusate. Data obtained in isolated perfused rat lungs in absence of blood carbonic anhydrase. Catalysis is result of activity of pulmonary vascular carbonic anhydrase.

From Bidani et al. 16
Figure 14. Figure 14.

Computed effect of erythrocyte permeability () and plasma catalysis (A0) of dehydration reaction on pulmonary CO2 exchange in resting human.

From Crandall and Bidani 29
Figure 15. Figure 15.

Kinetics of Haldane effect. Deoxygenated erythrocyte suspension was rapidly saturated (‐ ‐ ‐ ‐ ‐, right‐hand scale) and resulting liberation of CO2 (‐ ‐ ‐ ‐ ‐, left‐hand scale) monitored in continuous‐flow rapid‐reaction apparatus. Lower solid curve was obtained during carbonic anhydrase inhibition and represents carbamate formation. Upper solid curve was obtained without enzyme inhibition and represents sum of changes due to both oxylabile and carbamate.

From Klocke 86


Figure 1.

Pathways for hydration‐dehydration reaction. The k2–k′2 reaction is much faster than other two reactions, which are rate limiting for the process.



Figure 2.

Arrhenius plot illustrating effect of temperature on constants involved in CO2 reactions. Straight lines fitted to experimental data are given by Constant (log10) = m [103/T(°K)] + b; m and b values for each process are listed in figure.

Data for feoir from Pinsent et al. 118 and Sirs 138. Data for from Edsall 38. Data for from Roughton 129. Hydration constant Kh computed from and


Figure 3.

Effect of pH on Michaelis constant (Km; A) and turnover number (kcat; B) of human carbonic anhydrase I (HCA‐B) and II (HCA‐C) at 25°C and 0.2 M ionic strength. The pH variation of kcat/Km is result of changes in kcat because Km is constant over this pH range. The following buffers were used in the experiments: ▿, 3,5‐lutidine; ○, imidazole; □, N‐methylimidazole; Δ, 1,2‐dimethylimidazole.

From Khalifah 81


Figure 4.

Oscilloscopic tracing of change in pH after rapid mixing (STOP) of solution containing CO2 with 4 mM glycylglycine at 37°C. pHA, pH of glycylglycine solution prior to mixing. pHB, pH of mixture after mixing but prior to reaction. pHequil, carbamate equilibrium; subsequent pH change is due to continuing uncatalyzed hydration of CO2. pHc, extrapolation of pH to time of mixing; this pH would occur as result of carbamate formation alone.

From Gros et al. 60


Figure 5.

Carbamate dissociation curves of human plasma at 37°C.

From Gros et al. 60


Figure 6.

Carbon dioxide content of deoxygenated solutions of human Hb at constant partial pressure of CO2 (Pco2, 40 Torr). Upper curve obtained in absence of 2,3‐DPG; lower curve obtained after addition of 2 mol 2,3‐DPG/mol Hb tetramer.

From Bauer 10


Figure 7.

Influence of 2,3‐diphosphoglycerate (2,3‐DPG) on Haldane effect in erythrocytes. •, Data obtained with carbonic anhydrase inhibition, ▴, Data obtained without carbonic anhydrase inhibition. Relative contributions of (clear areas) and carbamate (shaded areas) to total Haldane effect are labeled.

Adapted from Klocke 86


Figure 8.

Carbon dioxide bound to β‐chain (A) and α‐chain (B) of Hb selectively carbamylated at NH2‐terminal amino groups. ○, □, Deoxygenated solutions. •, ▪, Solutions of Hb liganded with CO. ○, •, Solutions free of 2,3‐DPG. □, ▪, Data obtained in presence of 2 mol 2,3‐DPG/mol Hb tetramer.

From Perrella et al. 111. Reprinted by permission from Nature, copyright 1975, MacMillan Journals Limited


Figure 9.

Carbon dioxide dissociation curve of human blood plotted on linear (A) and logarithmic (B) axes.

Data from Christiansen et al. 27


Figure 10.

Reactions of CO2 in pulmonary capillary. CA, carbonic anhydrase, either free inside cell or bound to capillary endothelium. ‐ ‐>, Dehydration reaction proceeds much more slowly in plasma than erythrocyte. →, Processes that proceed rapidly. ‐‐‐>, Participation of H+ associated with Hb buffering.



Figure 11.

Variation in Haldane effect as function of extracellular pH at Pco2 of 42.5 Torr in erythrocyte suspensions. •, Data obtained with carbonic anhydrase inhibition. x, Data obtained without carbonic anhydrase inhibition. Contributions of oxylabile carbamate and to total Haldane effect are indicated.

From Klocke 86


Figure 12.

Carbon dioxide excretion () in isolated, blood‐free perfused rabbit lungs as function of perfusion rate (). ▴, Observed CO2 excretion. Δ, Expected excretion of CO2 dissolved in buffer, calculated from simultaneous measurements of excretion of acetylene dissolved in buffer. Shaded areas, CO2 generated in pulmonary capillary from contained in perfusate. Small amount of CO2 generated in presence of acetazolamide (B) is result of uncatalyzed dehydration reaction. Larger amount formed under control conditions (A) is due to catalysis of dehydration by capillary endothelial carbonic anhydrase.

From Klocke 89


Figure 13.

Lineweaver‐Burk plot of reciprocals of reaction velocity (V) and substrate () concentration in presence of different concentrations of acetazolamide (ACTZ). •, 12 mM in perfusate; ○, 25 mM in perfusate; ▴, 35 mM in perfusate. Data obtained in isolated perfused rat lungs in absence of blood carbonic anhydrase. Catalysis is result of activity of pulmonary vascular carbonic anhydrase.

From Bidani et al. 16


Figure 14.

Computed effect of erythrocyte permeability () and plasma catalysis (A0) of dehydration reaction on pulmonary CO2 exchange in resting human.

From Crandall and Bidani 29


Figure 15.

Kinetics of Haldane effect. Deoxygenated erythrocyte suspension was rapidly saturated (‐ ‐ ‐ ‐ ‐, right‐hand scale) and resulting liberation of CO2 (‐ ‐ ‐ ‐ ‐, left‐hand scale) monitored in continuous‐flow rapid‐reaction apparatus. Lower solid curve was obtained during carbonic anhydrase inhibition and represents carbamate formation. Upper solid curve was obtained without enzyme inhibition and represents sum of changes due to both oxylabile and carbamate.

From Klocke 86
References
 1. Altman, P. L., and D. S. Dittmer (editors). Respiration and Circulation. Bethesda, MD: Fed. Am. Soc. Exp. Biol., 1971, p. 211–217.
 2. Altman, P. L., J. F. Gibson, Jr., and C. C. Wang. Handbook of Respiration. Philadelphia, PA: Saunders, 1958, p. 64.
 3. Andersson, B., P. O. Nyman, and L. Strid. Amino acid sequence of human erythrocyte carbonic anhydrase B. Biochem. Biophys. Res. Commun. 48: 670–677, 1972.
 4. Antonini, E., and M. Brunori. Ligand‐dependent conformational changes. In: Hemoglobin and Myoglobin in Their Reactions with Ligands. New York: Elsevier, 1971, p. 135–152.
 5. Arnone, A. X‐ray studies of the interaction of CO2 with human deoxyhemoglobin. Nature Lond. 247: 143–145, 1974.
 6. Arnone, A., P. H. Rogers, and P. D. Briley. The binding of CO2 to human deoxyhemoglobin: an x‐ray study using low‐salt crystals. In: Biophysics and Physiology of Carbon Dioxide, edited by C. Bauer, G. Gros, and H. Bartels. New York: Springer‐Verlag, 1980, p. 67–74.
 7. Arturson, G., L. Garby, B. Wranne, and B. Zaar. Effect of 2,3‐diphosphoglycerate on the oxygen affinity and on the proton‐ and carbamino‐linked oxygen affinity of hemoglobin in human whole blood. Acta Physiol. Scand. 92: 332–340, 1974.
 8. Austin, W. H., E. Lacombe, P. W. Rand, and M. Chatterjee. Solubility of carbon dioxide in serum from 15 to 38 C. J. Appl. Physiol. 18: 301–304, 1963.
 9. Bauer, C. Antagonistic influence of CO2 and 2,3‐diphosphoglycerate on the Bohr effect of human haemoglobin. Life Sci. Part II Biochem. Gen. Mol. Biol. 8: 1041–1046, 1969.
 10. Bauer, C. Reduction of the carbon dioxide affinity of human haemoglobin solutions by 2,3‐diphosphoglycerate. Respir. Physiol. 10: 10–19, 1970.
 11. Bauer, C., R. Baumann, U. Engels, and B. Pacyna. The carbon dioxide affinity of various human hemoglobins. J. Biol. Chem. 250: 2173–2176, 1975.
 12. Bauer, C., and E. Schröder. Carbamino compounds of haemoglobin in human adult and foetal blood. J. Physiol. Lond. 229: 457–471, 1972.
 13. Benesch, R., and R. E. Benesch. The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin. Biochem. Biophys. Res. Commun. 26: 162–167, 1967.
 14. Bidani, A., E. D. Crandall, and R. E. Forster. Analysis of postcapillary pH changes in blood in vivo after gas exchange. J. Appl. Physiol. 44: 770–781, 1978.
 15. Bidani, A., R. W. Flumerfelt, and E. D. Crandall. Analysis of pulsatile capillary blood flow and volume on gas exchange. Respir. Physiol. 35: 27–42, 1978.
 16. Bidani, A., S. J. Mathew, and E. D. Crandall. Pulmonary vascular carbonic anhydrase activity. J. Appl. Physiol. 55: 75–83, 1983.
 17. Brazy, P. C., and R. B. Gunn. Furosemide inhibition of chloride transport in human red blood cells. J. Gen. Physiol. 68: 583–599, 1976.
 18. Brown, E. B., Jr., and R. L. Clancy. In vivo and in vitro CO2 blood buffer curves. J. Appl. Physiol. 20: 885–889, 1965.
 19. Bunn, H. F., and R. W. Briehl. The interaction of 2,3‐diphosphoglycerate with various human hemoglobins. J. Clin. Invest. 49: 1088–1095, 1970.
 20. Bursaux, E., C. Poyart, P. Guesnon, and B. Teisseire. Comparative effects of CO2 on the affinity for O2 of fetal and adult erythrocytes. Pfluegers Arch. 378: 197–203, 1979.
 21. Cabantchik, Z. I., and A. Rothstein. The nature of the membrane sites controlling anion permeability of human red blood cells as determined by studies with disulfonic stilbene derivatives. J. Membr. Physiol. 10: 311–330, 1972.
 22. Cabantchik, Z. I., and A. Rothstein. Membrane proteins related to anion permeability of human red blood cells. I. Localization of disulfonic stilbene binding sites in proteins involved in permeation. J. Membr. Biol. 15: 207–226, 1974.
 23. Cain, S. M., and A. B. Otis. Carbon dioxide transport in anesthetized dogs during inhibition of carbonic anhydrase. J. Appl. Physiol. 16: 1023–1028, 1961.
 24. Carter, M. J. Carbonic anhydrase: isoenzymes, properties, distribution, and functional significance. Biol. Rev. Camb. Philos. Soc. 47: 465–513, 1972.
 25. Chanutin, A., and R. R. Curnish. Effect of organic and inorganic phosphates on the oxygen equilibrium of human erythrocytes. Arch. Biochem. Biophys. 121: 96–102, 1967.
 26. Chow, E. I.‐H., E. D. Crandall, and R. E. Forster. Kinetics of bicarbonate‐chloride exchange across the human red blood cell membrane. J. Gen. Physiol. 68: 633–652, 1976.
 27. Christiansen, J., C. G. Douglas, and J. S. Haldane. The absorption and dissociation of carbon dioxide by human blood. J. Physiol. Lond. 48: 244–277, 1914.
 28. Coin, J. T., and J. S. Olson. The rate of oxygen uptake by human red blood cells. J. Biol. Chem. 254: 1178–1190, 1979.
 29. Crandall, E. D., and A. Bidani. Effects of red blood cell HCO3‐/Cl‐ exchange kinetics on lung CO2 transfer: theory. J. Appl. Physiol. 50: 265–271, 1981.
 30. Crandall, E. D., S. J. Mathew, R. S. Fleischer, H. I. Winter, and A. Bidani. Effects of inhibition of RBC HCO3‐/Cl‐ exchange on CO2 excretion and downstream pH disequilibrium in isolated rat lungs. J. Clin. Invest. 68: 853–862, 1981.
 31. Crandall, E. D., and J. E. O'Brasky. Direct evidence for participation of rat lung carbonic anhydrase in CO2 reactions. J. Clin. Invest. 62: 618–622, 1978.
 32. Crandall, E. D., H. I. Winter, J. D. Schaeffer, and A. Bidani. Effects of salicylate on HCO3‐/Cl‐ exchange across the human erythrocyte membrane. J. Membr. Biol. 65: 139–145, 1982.
 33. Dalmark, M. Effects of halides and bicarbonate on chloride transport in human red blood cells. J. Gen. Physiol. 67: 223–234, 1976.
 34. Dennard, A. E., and R. J. P. Williams. The catalysis of the reaction between carbon dioxide and water. J. Chem. Soc. Lond. A: 812–816, 1966.
 35. De Voe, H., and G. B. Kristiakowsky. The enzyme kinetics of carbonic anhydrase from bovine and human erythrocytes. J. Am. Chem. Soc. 83: 274–280, 1961.
 36. Dill, D. B., H. T. Edward, and W. V. Consolazio. Blood as a physicochemical system. XI. Man at rest. J. Biol. Chem. 118: 635–648, 1937.
 37. Donaldson, T. L., and J. A. Quinn. Kinetic constants determined from membrane transport measurements: carbonic anhydrase activity at high concentrations. Proc. Natl. Acad. Sci. USA 71: 4995–4999, 1974.
 38. Edsall, J. T. Carbon dioxide, carbonic acid, and bicarbonate ion: physical properties and kinetics of interconversion. In: CO2: Chemical, Biochemical, and Physiological Aspects, edited by R. E. Forster, J. T. Edsall, A. B. Otis, and F. J. W. Roughton. Washington, DC: NASA, 1969, SP–188, p. 15–27.
 39. Effros, R. M., R. S. Y. Chang, and P. Silverman. Acceleration of plasma bicarbonate conversion to carbon dioxide by pulmonary carbonic anhydrase. Science Wash. DC 199: 427–429, 1978.
 40. Effros, R. M., G. Mason, and P. Silverman. Role of perfusion and diffusion in 14CO2 exchange in the rabbit lung. J. Appl. Physiol. 51: 1136–1144, 1981.
 41. Effros, R. M., L. Shapiro, and P. Silverman. Carbonic anhydrase activity of rabbit lungs. J. Appl. Physiol. 49: 589–600, 1980.
 42. Effros, R. M., and M. L. Weissman. Carbonic anhydrase activity of the cat hind leg. J. Appl. Physiol. 47: 1090–1098, 1979.
 43. Eigen, M., K. Kustin, and G. Maass. Die Geschwindigkeit der Hydration von SO2 in wassriger Lösung. Z. Phys. Chem. 30: 130–136, 1961.
 44. Faurholt, C. Etudes sur les aqueuses de carbamates et de carbonates. J. Chim. Phys. 22: 1–44, 1925.
 45. Feisal, K. A., M. A. Sackner, and A. B. Du Bois. Comparison between the time available and the time required for CO2 equilibration in the lung. J. Clin. Invest. 42: 24–28, 1963.
 46. 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.
 47. Ferguson, J. K. W., and F. J. W. Roughton. The direct chemical estimation of carbamino compounds of CO2 with haemoglobin. J. Physiol. Lond. 83: 68–86, 1934.
 48. Fitzsimons, E. J., and J. Sendroy, Jr. Distribution of electrolytes in human blood. J. Biol. Chem. 236: 1595–1601, 1961.
 49. Forster, R. E. Rate of gas uptake by red cells. In: Handbook of Physiology. Respiration, edited by W. O. Fenn and H. Rahn. Washington, DC: Am. Physiol. Soc., 1964, sect. 3, vol. I, chapt. 32, p. 827–837.
 50. Forster, R. E. The rate of CO2 equilibrium between red cells and plasma. In: CO2 Chemical, Biochemical, and Physiological Aspects, edited by R. E. Forster, J. T. Edsall, A. B. Otis, and F. J. W. Roughton. Washington, DC: NASA, 1969, SP–188, p. 275–286.
 51. Forster, R. E., H. P. Constantine, M. R. Craw, H. H. Rotman, and R. A. Klocke. Reaction of CO2 with human hemoglobin solution. J. Biol. Chem. 243: 3317–3326, 1968.
 52. Forster, R. E., and E. D. Crandall. Time course of exchanges between red cells and extracellular fluid during CO2 uptake. J. Appl. Physiol. 38: 710–718, 1975.
 53. Garby, L., and C.‐H. De Verdier. 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.
 54. Garby, L., M. Robert, and B. Zaar. Proton‐ and carbamino‐linked oxygen affinity of normal human blood. Acta Physiol. Scand. 84: 482–492, 1972.
 55. Goldman, D. E. Potential, impedence and rectification in membranes. J. Gen. Physiol. 27: 37–60, 1943.
 56. Grant, B. J. B. Influence of Bohr‐Haldane effect on steady‐state gas exchange. J. Appl. Physiol. 52: 1330–1337, 1982.
 57. Gray, B. A. The rate of approach to equilibrium in uncatalyzed CO2 hydration reactions: the theoretical effect of buffering capacity. Respir. Physiol. 11: 223—234, 1971.
 58. Gray, R. D. The kinetics ofthe alkaline Bohr effect of human hemoglobin. J. Biol. Chem. 245: 2914–2921, 1970.
 59. Gros, G., and C. Bauer. High p K value of the N‐terminal amino group of the γ‐chain causes low CO2 binding of human fetal hemoglobin. Biochem. Biophys. Res. Commun. 80: 56–62, 1978.
 60. Gros, G., R. E. Forster, and L. Lin. The carbamate reaction of glycylglycine, plasma, and tissue extracts evaluated by a pH stopped flow apparatus. J. Biol. Chem. 251: 4398–4407, 1976.
 61. Gros, G., and W. Moll. The diffusion of carbon dioxide in erythrocytes and hemoglobin solutions. Pfluegers Arch. 324: 249–266, 1971.
 62. Gros, G., H. S. Rollema, and R. E. Forster. The carbamate equilibrium of α‐ and ε‐amino groups of human hemoglobin at 37°C. J. Biol. Chem. 256: 5471–5480, 1981.
 63. Gunn, R. B., M. Dalmark, D. C. Tosteson, and J. O. Wieth. Characteristics of chloride transport in human red blood cells. J. Gen. Physiol. 61: 185–206, 1973.
 64. Gunn, R. B., and O. Fröhlich. Asymmetry in the mechanism for anion exchange in human red blood cell membranes. J. Gen. Physiol. 74: 351–374, 1979.
 65. Gutknecht, J., M. A. Bisson, and F. C. Tosteson. Diffusion of carbon dioxide through lipid bilayer membranes: effects of carbonic anhydrase, bicarbonate, and unstirred layers. J. Gen. Physiol. 69: 779–794, 1977.
 66. Hamburger, H. J. Anionenwanderungen in serum und Blut unter dem Einfluss von CO2, Säure und Alkali. Biochem. Z. 86: 309–324, 1918.
 67. Henderson, L. E., D. Henriksson, and P. O. Nyman. Primary structure of human carbonic anhydrase C. J. Biol. Chem. 251: 5457–5463, 1976.
 68. Henriques, O. M. Die Bindungsweise des Kohlendioxyds im Blute. Biochem. Z. 200: 1–24, 1928.
 69. Hill, E. P., G. G. Power, and L. D. Longo. Mathematical simulation of pulmonary O2 and CO2 exchange. Am. J. Physiol. 224: 904–917, 1973.
 70. Hlastala, M. P. Significance ofthe Bohr and Haldane effects in the pulmonary capillary. Respir. Physiol. 17: 81–92, 1973.
 71. Hlastala, M. P., and R. D. Woodson. Saturation dependency of the Bohr effect: interactions among H+, CO2, and DPG. J. Appl. Physiol. 38: 1126–1131, 1975.
 72. Holland, R. A. B., and R. E. Forster II. Effect of temperature on rate of CO2 uptake by human red cell suspensions. Am. J. Physiol. 228: 1589–1596, 1975.
 73. Holmes, R. S. Mammalian carbonic anhydrase isoenzymes: evidence for a third locus. J. Exp. Zool. 197: 289–295, 1976.
 74. Holmes, R. S. Purification, molecular properties and ontogeny of carbonic anhydrase isoenzymes. Eur. J. Biochem. 78: 511–520, 1977.
 75. Hyde, R. W., R. J. M. Puy, W. F. Raub, and R. E. Forster. Rate of disappearance of labeled carbon dioxide from the lungs of humans during breath holding: a method for studying the dynamics of pulmonary CO2 exchange. J. Clin. Invest. 47: 1535–1552, 1968.
 76. Itada, N., and R. E. Forster. Carbonic anhydrase activity in intact red blood cells measured with lsO exchange. J. Biol. Chem. 252: 3881–3890, 1977.
 77. Jeffery, S., Y. Edwards, and N. Carter. Distribution of CAIII in fetal and adult human tissue. Biochem. Genet. 18: 843–849, 1980.
 78. Keilin, D., and T. Mann. Carbonic anhydrase. Purification and nature ofthe enzyme. Biochem. J. 34: 1163–1176, 1940.
 79. Kernohan, J. C., W. W. Forrest, and F. J. W. Roughton. The activity of concentrated solutions of carbonic anhydrase. Biochim. Biophys. Acta 67: 31–41, 1963.
 80. Kernohan, J. C., and F. J. W. Roughton. Thermal studies of the rates of the reactions of carbon dioxide in concentrated haemoglobin solutions and in red blood cells. A. The reactions catalysed by carbonic anhydrase. B. The carbamino reactions of oxygenated and deoxygenated haemoglobin. J. Physiol. Lond. 197: 345–361, 1968.
 81. Khalifah, R. G. The carbon dioxide hydration activity of carbonic anhydrase. Stop‐flow kinetic studies on the native human isoenzymes B and C. J. Biol. Chem. 246: 2561–2573, 1971.
 82. Khalifah, R. G. Carbon dioxide hydration activity of carbonic anhydrase: paradoxical consequences of the unusually rapid catalysis. Proc. Natl. Acad. Sci. USA 70: 1986–1989, 1973.
 83. Kilmartin, J. V., J. Fogg, M. Luzzana, and L. Rossi‐Bernardi. Role of the α‐amino groups of the α and ã chains of human hemoglobin in oxygen‐linked binding of carbon dioxide. J. Biol. Chem. 248: 7039–7043, 1973.
 84. Kilmartin, J. V., and L. Rossi‐Bernardi. The binding of carbon dioxide by horse haemoglobin. Biochem. J. 124: 31–45, 1971.
 85. Klocke, R. A. Influence of oxygenation, pH, and 2,3‐diphosphoglycerate on carbon dioxide exchange. Chest 61, Suppl.: 20S–22S, 1972.
 86. Klocke, R. A. Mechanism and kinetics of the Haldane effect in human erythrocytes. J. Appl. Physiol. 35: 673–681, 1973.
 87. Klocke, R. A. Rate of bicarbonate‐chloride exchange in human red cells at 37°C. J. Appl. Physiol. 40: 707–714, 1976.
 88. Klocke, R. A. Carbon dioxide transport. In: Lung Biology in Health and Disease. Extrapulmonary Manifestations of Respiratory Disease, edited by E. D. Robin. New York: Dekker, 1978, vol. 8, chapt. 9, p. 315–343.
 89. Klocke, R. A. Catalysis of CO2 reactions by lung carbonic anhydrase. J. Appl. Physiol. 44: 882–888, 1978.
 90. Klocke, R. A. Equilibrium of CO2 reactions in the pulmonary capillary. J. Appl. Physiol. 48: 972–976, 1980.
 91. Klocke, R. A. Kinetics of pulmonary gas exchange. In: Pulmonary Gas Exchange. Ventilation, Blood Flow, and Diffusion, edited by J. B. West. New York: Academic, 1980, vol. 1, p. 174–218.
 92. Klocke, R. A., and F. Flasterstein. Kinetics of erythrocyte penetration by aliphatic acids. J. Appl. Physiol. 53: 1138–1143, 1982.
 93. Knauf, P. Erythrocyte anion exchange and the band 3 protein: transport kinetics and molecular structure. In: Current Topics in Membranes and Transport, edited by F. Bronner and A. Kleinzeller. New York: Academic, 1979, vol. 12, p. 249–363.
 94. Knoche, W. Chemical reactions of CO2 in water. In: Biophysics and Physiology of Carbon Dioxide, edited by C. Bauer, G. Gros, and H. Bartels. New York: Springer‐Verlag, 1980, p. 3–11.
 95. Koester, M. K., A. M. Register, and E. A. Noltmann. Basic muscle protein: a third genetic locus isoenzyme of carbonic anhydrase. Biochem. Biophys. Res. Commun. 76: 196–204, 1977.
 96. Lassen, U. V. Membrane potential and membrane resistance of red cells. In: Oxygen Affinity of Hemoglobin and Red Cell Acid Base Status, edited by P. Astrup and M. Rørth. New York: Academic, 1972, p. 291–306. (Alfred Benzon Symp., 4th, 1971.)
 97. Liljas, A., K. K. Kannan, P.‐C. Bergstén, I. Waara, K. Fridborg, B. Strandberg, U. Carlbom, L. Järup, S. Lövgren, and M. Petef. Crystal structure of human carbonic anhydrase C. Nature Lond. New Biol. 235: 131–137, 1972.
 98. Lönnerholm, G. Pulmonary carbonic anhydrase in the human, monkey, and rat. J. Appl. Physiol. 52: 352–356, 1982.
 99. Maren, T. H. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol. Rev. 47: 595–781, 1967.
 100. Maren, T. H., C. S. Rayburn, and N. E. Liddell. Inhibition by anions of human red cell carbonic anhydrase B: physiological and biochemical implications. Science Wash. DC 191: 469–472, 1976.
 101. Matthew, J. B., J. S. Morrow, R. J. Wittebort, and F. J. N. Gurd. Quantitative determination of carbamino adducts of α and ã chains in human adult hemoglobin in presence and absence of carbon monoxide and 2,3‐diphosphoglycerate. J. Biol. Chem. 252: 2234–2244, 1977.
 102. McHardy, G. J. R. The relationship between the differences in pressure and content of carbon dioxide in arterial and venous blood. Clin. Sci. Lond. 32: 299–309, 1967.
 103. Meldrum, N. U., and F. J. W. Roughton. Carbonic anhydrase. Its preparation and properties. J. Physiol. Lond. 80: 113–142, 1933.
 104. Morrow, J. S., J. B. Matthew, R. S. Wittebort, and F. R. N. Gurd. Carbon 13 resonances of 13CO2 carbamino adducts of α and ã chains in human adult hemoglobin. J. Biol. Chem. 251: 477–484, 1976.
 105. Nichols, G., Jr. Serial changes in tissue carbon dioxide content during acute respiratory acidosis. J. Clin. Invest. 37: 1111–1122, 1958.
 106. O'Brasky, J. E., and E. D. Crandall. Organ and species differences in tissue vascular carbonic anhydrase activity. J. Appl. Physiol. 49: 211–217, 1980
 107. O'Brasky, J. E., T. Mauro, and E. D. Crandall. Postcapillary pH disequilibrium after gas exchange in isolated perfused liver. J. Appl. Physiol. 47: 1079–1083, 1979.
 108. Passow, H. Passive ion permeability of the erythrocyte membrane. Prog. Biophys. Mol. Biol. 19: 425–467, 1969.
 109. Perrella, M., D. Bresciana, and L. Rossi‐Bernardi. The binding of CO2 to human hemoglobin. J. Biol. Chem. 250: 5413–5418, 1975.
 110. Perrella, M., G. Guglielmo, and A. Mosca. Determination of the equilibrium constants for oxygen‐linked CO2 binding to human hemoglobin. FEBS Lett. 78: 287–290, 1977.
 111. Perrella, M., J. V. Kilmartin, J. Fogg, and L. Rossi‐Bernardi. Identification of the high and low affinity CO2‐binding sites of human haemoglobin. Nature Lond. 256: 759–761, 1975.
 112. Perrella, M., L. Rossi‐Bernardi, and F. J. W. Roughton. The carbamate equilibrium between CO2 and bovine haemoglobin at 25°C. In: Oxygen Affinity of Hemoglobin and Red Cell Acid Base Status, edited by P. Astrup and M. Rørth. New York: Academic, 1972, p. 177–207. (Alfred Benzon Symp., 4th, 1971.)
 113. Perutz, M. F., H. Muirhead, L. Mazzarella, R. A. Crowther, J. Greer, and J. V. Kilmartin. Identification of residues responsible for the alkaline Bohr effect in haemoglobin. Nature Lond. 222: 1240–1243, 1969.
 114. Peters, J. P. Studies of the carbon dioxide absorption curve of human blood. III. A further discussion of the form of the absorption curve plotted logarithmically, with a convenient type of interpolation chart. J. Biol. Chem. 56: 745–750, 1923.
 115. Peters, J. P., H. A. Bulger, and A. J. Eisenman. Studies of the carbon dioxide absorption curve of human blood. IV. The relation of the hemoglobin content of blood to the form of the carbon dioxide absorption curve. J. Biol. Chem. 58: 747–768, 1924.
 116. Peters, J. P., H. A. Bulger, and A. J. Eisenman. Studies of the carbon dioxide absorption curve of human blood. V. The construction of the CO2 absorption curve from one observed point. J. Biol. Chem. 58: 769–771, 1924.
 117. Piiper, J. Rates of chloride‐bicarbonate exchange between red cells and plasma. In: CO2 Chemical, Biochemical, and Physiological Aspects, edited by R. E. Forster, J. T. Edsall, A. B. Otis, and F. J. W. Roughton. Washington, DC: NASA, 1969, SP–188, p. 267–273.
 118. Pinsent, B. R. W., L. Pearson, and F. J. W. Roughton. The kinetics of carbon dioxide with hydroxide ions. Trans. Faraday Soc. 52: 1512–1520, 1956.
 119. Plewes, J. L., A. J. Olszowka, and L. E. Farhi. Amount and rates of CO2 storage in lung tissue. Respir. Physiol. 28: 359–370, 1976.
 120. Pocker, Y., and D. W. Bjorkquist. Comparative studies of bovine carbonic anhydrase in H2O and D2O. Stopped‐flow studies of the kinetics of interconversion of CO2 and HCO3. Biochemistry 16: 5698–5707, 1977.
 121. Pocker, Y., and S. Sarkanen. Carbonic anhydrase: structure, catalytic versatility, and inhibition. Adv. Enzymol. Relat. Areas Mol. Biol. 47: 149–274, 1978.
 122. Reeves, R. B. Temperature‐induced changes in blood acid‐base status: Donnan rcl and red cell volume. J. Appl. Physiol. 40: 762–767, 1976.
 123. Ridderstråle, Y. Observations on the localization of carbonic anhydrase in muscle. Acta Physiol. Scand. 106: 239–240, 1979.
 124. Rispens, P., C. W. Dellebarre, D. Eleveld, W. Helder, and W. G. Zijlstra. The apparent first dissociation constant of carbonic acid in plasma between 16 and 42.5°. Clin. Chim. Acta 22: 627–637, 1968.
 125. Rodkey, F. L., H. A. Collison, J. D. O'Neal, and J. Sendroy, Jr. Carbon dioxide absorption curves of dog blood and plasma. J. Appl. Physiol. 30: 178–185, 1971.
 126. Rossi‐Bernardi, L., and F. J. W. Roughton. The specific influence of carbon dioxide and carbamate compounds on the buffer power and Bohr effects in human haemoglobin solutions. J. Physiol. Lond. 189: 1–29, 1967.
 127. Rothstein, A., Z. I. Cabantchik, and P. Knauf. Mechanism of anion transport in red blood cells: role of membrane proteins. Federation Proc. 35: 3–10, 1976.
 128. Roughton, F. J. W. Recent work on carbon dioxide transport by the blood. Physiol. Rev. 15: 241–296, 1935.
 129. Roughton, F. J. W. Transport of oxygen and carbon dioxide. In: Handbook of Physiology. Respiration, edited by W. O. Fenn and H. Rahn. Washington, DC: Am. Physiol. Soc., 1964, sect. 3, vol. I. chapt. 31, p. 767–825.
 130. Roughton, F. J. W. Some recent work on the interactions of oxygen, carbon dioxide and haemoglobin. Biochem. J. 117: 801–812, 1970.
 131. Ryan, U. S., P. L. Whitney, and J. W. Ryan. Localization of carbonic anhydrase on pulmonary artery endothelial cells in culture. J. Appl. Physiol. 53: 914–919, 1982.
 132. Savitz, D., V. W. Sidel, and A. K. Solomon. Osmotic properties of human red cells. J. Gen. Physiol. 48: 79–94, 1964.
 133. Shaw, L. A., and A. C. Messer. The transfer of bicarbonate between the blood and tissues caused by alterations of the carbon dioxide concentration in the lungs. Am. J. Physiol. 100: 122–136, 1932.
 134. Siggaard‐Andersen, O. Oxygen‐linked hydrogen ion 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.
 135. Silverman, D. N., and C. K. Tu. Buffer dependence of carbonic anhydrase catalyzed oxygen‐18 exchange at equilibrium. J. Am. Chem. Soc. 97: 2263–2269, 1975.
 136. Silverman, D. N., C. K. Tu, and N. Roessler. Diffusion‐limited exchange of 18O between CO2 and water in red cell suspensions. Respir. Physiol. 44: 285–298, 1981.
 137. Silverman, D. N., C. K. Tu, and G. C. Wynns. Depletion of 18O from C18O2 in erythroycte suspensions. The permeability of the erythrocyte membrane to CO2. J. Biol. Chem. 251: 4428–4435, 1976.
 138. Sirs, J. A. Electrometric stopped flow measurements of rapid reactions in solution. Part 1. Conductivity measurements. Trans. Faraday Soc. 54: 201–206, 1958.
 139. Soni, J., K. A. Feisal, and A. B. Du Bois. The rate of intrapulmonary blood gas exchange in living animals. J. Clin. Invest. 42: 16–23, 1963.
 140. Stadie, W. C., and H. O'Brien. The catalysis of the hydration of carbon dioxide and dehydration of carbamic acid by an enzyme isolated from red blood cells. J. Biol. Chem. 103: 521–529, 1933.
 141. Swenson, E. R., and T. H. Maren. A quantitative analysis of CO2 transport at rest and during maximal exercise. Respir. Physiol. 35: 129–159, 1978.
 142. Visser, B. F. Pulmonary diffusion of carbon dioxide. Phys. Med. Biol. 5: 155–166, 1960.
 143. Wagner, P. D. Diffusion and chemical reaction in pulmonary gas exchange. Physiol. Rev. 57: 257–312, 1977.
 144. Wagner, P. D., and J. B. West. Effects of diffusion impairment on O2 and CO2 time courses in pulmonary capillaries. J. Appl. Physiol. 33: 62–71, 1972.
 145. Wyman, J. Linked functions and reciprocal effects in haemoglobin: a second look. Adv. Protein Chem. 19: 223–286, 1964.
 146. Zander, R., and H. Schmid‐Schönbein. Intracellular mechanisms of oxygen transport in flowing blood. Respir. Physiol. 19: 279–289, 1973.
 147. Zborowska‐Sluis, D. T., A. L'Abbate, and G. A. Klassen. Evidence of carbonic anhydrase activity in skeletal muscle: a role for facilitative carbon dioxide transport. Respir. Physiol. 21: 341–350, 1974.
 148. Zborowska‐Sluis, D. T., A. L'Abbate, R. R. Mildenberger, and G. A. Klassen. The effect of acetazolamide on myocardial carbon dioxide space. Respir. Physiol. 23: 311–316, 1975.

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Article Title: Carbon Dioxide Transport
 

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Robert A. Klocke. Carbon Dioxide Transport. Compr Physiol 2011, Supplement 13: Handbook of Physiology, The Respiratory System, Gas Exchange: 173-197. First published in print 1987. doi: 10.1002/cphy.cp030410