Acid-Base and Energy Metabolism of the Brain in Hypercapnia and Hypocapnia

  • Bo K. Siesjö
  • Jaroslava Folbergrová
  • Kenneth Messeter
Part of the Topics In Environmental Physiology And Medicine book series (TEPHY)

Abstract

The metabolism of brain tissue shows some characteristic and specific features (for details and further references, see MCILWAIN [1966], BACHELARD and MCILWAIN [1969], BALACZ [1970]). Thus the organ is active continuously, and in spite of its small weight it is responsible for about 20% of the resting oxygen consumption of the body. Further, although isolated brain tissues can oxidize a variety of substrates in vitro, only glucose can normally pass the blood-brain barrier with sufficient speed to maintain the energy requirements in vivo. Measurements of arteriovenous differences for glucose, oxygen, and carbon dioxide show that the respiratory quotient is close to unity, thus confirming that glucose is the sole substrate. These measurements show that about 95% of the glucose consumed is oxidized to carbon dioxide. The rest of the glucose (about 5%) appears as an arteriovenous difference for lactate (see COHEN [1971]). However, the arteriovenous balance does not reveal the rapid interconversion of glucose carbon between the tricarboxylic acid cycle and the glutamate group of amino acids. In fact, as much as 30% of the 14C administered in radioactive glucose may label these acids (aspartate, glutamate, glutamine, and λ aminobutyrate), but since an equivalent amount of amino acid carbon is fed into the Krebs cycle the end result is compatible with simple glucose oxidation (ROBERTS et al. [1959], VRBA [1962], see also TOWER [1960], BACHELARD [1965]). The rapid turnover of the glutamate group of amino acids, which is partly specific for the brain, may be related to the fact that some of the acids function as excitatory or inhibitory transmitters.

Keywords

Adenosine Barium Bicarbonate Glutamine Neurol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Bibliography

  1. Atkinson, D. E., “The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers”. Bio. chem. 7:4030–34 (1968).Google Scholar
  2. Alexander, S. C., Smith, T. C., Strobel, G., Stephen, G. W., and Wollman, H., “Cerebral carbohydrate metabolism of man during respiratory and metabolic alkalosis.” J. Appl. Physiol 24:66–72.Google Scholar
  3. Bachelard, H. S., “Glucose metabolism and a-keto-acids in rat brain and liver in vivo.” Nature 205:903–04 (1965).CrossRefGoogle Scholar
  4. Bachelard, H. S., and Mcllwain, H., “Carbohydrate and oxidative metabolism in neural systems.” In Comprehensive biochemistry. Vol. 17. M. Florkin and E. H. Stotz, eds. Amsterdam: Elsevier (1969).Google Scholar
  5. Bain, J. A., and Klein, J. R., “Effect of carbon dioxide on brain glucose, lactate, pyruvate and phosphates.” Am. J. Physiol 158:478–84 (1949).PubMedGoogle Scholar
  6. Balacz, R., “Carbohydrate metabolism.” In Handbook of neurochemistry. A. Lajtha, ed. New York: Plenum Press (1970).Google Scholar
  7. Berl, S., Takagaki, G., Clarke, D. D., and Waelsch, H., “Carbon dioxide fixation in the brain.” J. Biol Chem. 237:2570–73 (1962).PubMedGoogle Scholar
  8. Berl, S., Takagaki, G., Clarke, D. D., and Waelsch, H., Cheng, S.-C., and Waelsch, H., “Carbon dioxide fixation in vertebrate and invertebrate nervous tissue. In Comparative Neurochemistry. D. Richter, ed. New York: Pergamon Press (1964).Google Scholar
  9. Brzezinski, J., Kjällquist, Å., and Siesjö, B. K., “Mean carbon dioxide tension in the brain after carbonic anhydrase inhibition.” J. Physiol (London) 188:12–23.Google Scholar
  10. Butler, T. C., Waddell, W. J., and Poole, D. T., “Intracellular based on the distribution of electrolytes.” Federation Proc. 26:1327–32 (1967).Google Scholar
  11. Bücher, T. H., and Klingenberg, M., “Wege des Wasserstoffs in der lebendigen Organisation.” Angew. Chem. 70:552–70 (1958).CrossRefGoogle Scholar
  12. Cameron, I. R., Davson, H., and Segal, M. B., “The effect of hypercapnia on the blood—brain barrier permeability to sucrose in the rabbit.” Yale J. Biol Med. 42:241–47 (1970).Google Scholar
  13. Caldwell, P. C., “Intracellular pH.” Intern. Rev. Cytol. 5:229–77 (1956).CrossRefGoogle Scholar
  14. Caldwell, P. C., “Studies on the internal of large muscle and nerve fibres.” J. Physiol (London) 142:22–62 (1958).PubMedGoogle Scholar
  15. Carter, N. W., Rector, F. C., Jr., and Seldin, D. W., “Measurement of intracellular of skeletal muscle with sensitive glass microelectrodes.” J. Clin. Invest. 46:920–33 (1967).PubMedCrossRefGoogle Scholar
  16. Cohen, P. J., “Energy metabolism of the human brain.” In Ion homeostasis of the brain. B. K. Siesjö and S. C. Sørensen, eds. Copenhagen: Munksgaard (1971).Google Scholar
  17. Conway, E. J., and Fearon, P. J., “The acid-labile CO 2 in mammalian muscle and the pH of the muscle fibre.” J. Physiol (London) 103:274–89 (1944).PubMedGoogle Scholar
  18. Conway, E. J., and Fearon, P. J. “Nature and significance of concentration relations of potassium and sodium ions in skeletal muscle.” Physiol Rev. 37:84–132 (1957).PubMedGoogle Scholar
  19. Danielson, I. S., Chu, H. I., and Hastings, A. B., “The pK′ of carbonic acid in concentrated protein solutions and muscle.” J. Biol Chem. 131:243–57 (1939).Google Scholar
  20. Danielson, I. S., Chu, H. I., and Hastings, A. B., and Hastings, A. B., “A method for determining carbon dioxide.” J. Biol Chem. 130:349–56 (1939).Google Scholar
  21. Deicher, H. K, and Shipp, J. C., “Effect of pH, Pco2 and bicarbonate on metabolism of glucose by perfused rat heart.” Biochim. Biophys. Acta 121:250–60 (1966).Google Scholar
  22. Domonkos, J., and Huszak, I., “Effect of hydrogen ion concentration on the carbohydrate metabolism of brain tissue.” J. Neurochem. 4:238–43 (1959).PubMedCrossRefGoogle Scholar
  23. Edsall, J. T., and Wyman, J., Biophysical Chemistry, Vol. 1. New York: Academic Press (1958).Google Scholar
  24. Everett, N. B., Simmons, B., and Lasher, E. P., “Distribution of blood (Fe59) and plasma volumes of rats determined by liquid nitrogen freezing.” Circulat. Res. 4:419–24 (1956).PubMedGoogle Scholar
  25. Fanestil, D. D., Hastings, A. B., and Mahowald, T. A., “Environmental CO2 stimulation of mitochondrial adenosine triphosphate activity.” Biol. Chem. 238:836–40 (1963).Google Scholar
  26. Fencl, V., Miller, T. B., and Pappenheimer, J. R., “Studies on the respiratory response to disturbances of acid-base balance, with deductions concerning the ionic composition of cerebral interstitial fluid.” Am. J. Physiol. 210:459–72 (1966).PubMedGoogle Scholar
  27. Geiger, A., “Metabolism and function in the brain.” In Neurochemistry. K. A. C. Elliot, I. H. Page, and J. H. Quastel, eds. Springfield: Charles C. Thomas (1962).Google Scholar
  28. Granholm, L., and Siesjö, B. K., “The effects of hypercapnia and hypocapnia upon the cerebrospinal fluid lactate and pyruvate concentrations and upon the lactate, pyruvate, ATP, ADP, phosphocreatine and creatine concentrations of cat brain tissue.” Acta Physiol. Scand. 75:257–66 (1969).PubMedCrossRefGoogle Scholar
  29. Granholm, L., and Siesjö, B. K., and Siesjö, B. K., “The effect of combined respiratory and nonrespiratory alkalosis on energy metabolites and acid-base parameters in the rat brain.” Acta Physiol. Scand. 81:307–14 (1971).PubMedCrossRefGoogle Scholar
  30. Hohorst, H. J., Kreuz, F. H., and Bucher, T., “Uber Metabolitgehalte und Metabolit—Konzentrationen in der Leber der Ratte.” Biochem. Z. 332:18–46 (1959).PubMedGoogle Scholar
  31. Huckabee, W. E., In Effects of Anesthesia on metabolism and cellular functions. J. P. Bunker and L. D. Vandam, eds. Pharmacol. Rev. 17:183, pp. 247–52 (1965).Google Scholar
  32. Kasbekar, D. K., “Effect of carbon dioxide—bicarbonate mixtures on rat liver mitochondrial oxidative phosphorylation.” Bio- chim. Biophys. Acta, 128:205–08 (1966).Google Scholar
  33. Kety, S. S., and Schmidt, C. F., “The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men.” J. Clin. Invest. 27:484–91 (1948).CrossRefGoogle Scholar
  34. Kjällquist, Å., Nardini, M., and Siesjö, B. K., “The regulation of extra- and intracellular acid-base parameters in the rat brain during hyper- and hypocapnia. Acta Physiol. Scand. 76:485–94 (1969).PubMedCrossRefGoogle Scholar
  35. Kostyuk, P. G., and Sorokina, Z. A., “On the mechanism of hydrogen ion distribution between cell protoplasm and the medium.” Membrane Proc. Symp., Prague. New York: Academic Press (1961).Google Scholar
  36. Krebs, H. A., and Kornberg, H. L., Energy transformation in living matter. Berlin: Springer Verlag (1957).Google Scholar
  37. Kuby, S. A., and Noltmann, E. A., “ATP-creatine transphosphorylase.” In The enzymes, Vol. 6. New York: Academic Press (1962).Google Scholar
  38. Lehninger, A. L., Biochemistry. New York: Worth Publishers (1970).Google Scholar
  39. Leusen, I., Lacroix, E., and Demeester, G., “Lactate and pyruvate in the brain of rats during changes in acid-base balance.” Arch. Internat. Physiol. Biochem. 75:310–24 (1967).CrossRefGoogle Scholar
  40. Leusen, I., Lacroix, E., and Demeester, G., and Demeester, G., “Lactate and pyruvate in the brain of rats during hyperventilation.” Arch. Internat. Physiol. Biochem. 74:25–34 (1966).CrossRefGoogle Scholar
  41. Lowry, O. H., and Passonneau, J. V., “Kinetic evidence for multiple binding sites on phosphofructokinase.” J. Biol. Chem. 241: 2268–79 (1966).PubMedGoogle Scholar
  42. Mcllwain, H., Biochemistry and the central nervous system. London: J. & A. Churchill Ltd. (1966).Google Scholar
  43. Messeter, K., and Siesjö, B. K., “Regulation of intracellular pH in the rat brain in chronic hypercapnia.” Acta Physiol. Scand. 79:136–38 (1970).PubMedCrossRefGoogle Scholar
  44. Messeter, K., and Siesjö, B. K., “Regulation of the CSF in acute and sustained respiratory acidosis.” Acta Physiol. Scand. 83:21–30 (1971).PubMedCrossRefGoogle Scholar
  45. Messeter, K., and Siesjö, B. K., “The intracellular pH′ in the brain in acute and sustained hypercapnia. Acta Physiol. Scand. 83:210–219 (1971).PubMedCrossRefGoogle Scholar
  46. Messeter, K., and Siesjö, B. K., “The effect of acute and chronic hypercapnia upon the lactate, pyruvate, α-ketoglutarate, and glutamate contents of the rat brain.” Acta Physiol. Scand. 83:344–351 (1971).PubMedCrossRefGoogle Scholar
  47. Navon, S., and Agrest, A., “ATP content in the central nervous system of rats exposed to chronic hypercapnia.” Am. J. Physiol. 205: 957–58 (1963).PubMedGoogle Scholar
  48. Nilsson, L., and Siesjö, B. K., “The effect of hypoxia upon labile substrates and upon acid-base parameters in the brain.” In Ion homeostasis of the brain. B. K. Siesjö and S. C. Sørensen, eds. Copenhagen: Munks-gaard (1971).Google Scholar
  49. Paillard, M., Sraer, J. D., and Leviel, J. D., Direct measurement of intracellular in rat and crab muscle in vitro. Abstract, Fifth Annual Meeting, European Society for Clinical Investigation. April 1971.Google Scholar
  50. Plum, F., and Posner, J. B., “Blood and cerebrospinal fluid lactate during hyperventilation.” Am. J. Physiol. 212:864–70 (1967).PubMedGoogle Scholar
  51. Plum, F., and Posner, J. B., Posner, J. B., and Smith, W. W., “Effect of hyperbaric-hyperoxic hyperventilation on blood, brain, and CSF lactate.” Am. J. Physiol. 215:1240–44 (1968).PubMedGoogle Scholar
  52. Pontén, U., and Siesjö, B. K., “A method for the determination of the total carbon dioxide content of frozen tissues.” Acta Physiol. Scand. 60:297–308 (1964).PubMedCrossRefGoogle Scholar
  53. Pontén, U., and Siesjö, B. K., “Gradients of CO2 tension in the brain.” Acta Physiol. Scand. 68:152–63 (1966).CrossRefGoogle Scholar
  54. Rall, D. P., and Fenstermacher, J. D., “Volume of cerebral extracellular fluids.” In Ion homeostasis of the brain. B. K. Siesjö and S. C. Sørensen, eds. Copenhagen: Munks-gaard (1971).Google Scholar
  55. Roberts, R. B., Flexner, J. B., and Flexner, L. B., “Biochemical and physiological differentiation during morphogenesis—XXIII.” J. Neurochem. 4:78–99 (1959).PubMedCrossRefGoogle Scholar
  56. Robson, J. S., Bone, J. M., and Lambie, A. T., “Intracellular pH.” In Advances in clinical chemistry. Vol. 2. O. Bodansky and C. P. Stewart, eds. New York: Academic Press (1968).Google Scholar
  57. Reivich, M., Dickson, J., Clark, J., Hedden, M., and Lambertsen, C. J., “Role of hypoxia in cerebral circulatory and metabolic changes during hypocarbia in man: studies in hyperbaric milieu.” In CBF & CSF. D. H. Ingvar, N. A. Lassen, B. K. Siesjö, and E. Skinhoj, eds. Scand. J. Clin. Lab. Invest. Suppl. 102. IV:B (1968).Google Scholar
  58. Scheuer, J., and Berry, M. N., “Effect of alkalosis on glycolysis in the isolated rat heart.” Am. J. Physiol. 213:1143–48 (1967).PubMedGoogle Scholar
  59. Siesjö, B. K., “The solubility of carbon dioxide in cerebral cortical tissue of cats. With a note on the solubility of carbon dioxide in water, 0.16 M Nl and cerebrospinal fluid.” Acta Physiol. Scand. 55:325–41 (1962a).PubMedCrossRefGoogle Scholar
  60. Siesjö, B. K., “The bicarbonate/carbonic acid buffer system of the cerebral cortex of cats as studied in tissue homogenates. 2. The pK′I of carbonic acid at 37.5°C, and the relation between carbon dioxide tension and. pH.” Acta Neurol. Scand. 38:121–41 (1962b).PubMedCrossRefGoogle Scholar
  61. Siesjö, B. K., “Quantification of pH regulation in hypercapnia and hypocapnia.” Scand. J. Clin. Lab. Invest. 28:113–119 (1971).PubMedCrossRefGoogle Scholar
  62. Siesjö, B. K., and Messeter, K., “Factors determining intracellular pH.” In Ion homeostasis of the brain. B. K. Siesjö and S. C. Sørensen, eds. Copenhagen: Munksgaard (1971).Google Scholar
  63. Siesjö, B. K., Nilsson, L., Rokeach, M., and Zwetnow, N. N., “Energy metabolism of the brain at reduced cerebral perfusion pressures and in arterial hypoxemia.” In Brain hypoxia. J. B. Brierley, ed. Heinemann Medical (1971).Google Scholar
  64. Tower, D. B., Neurochemistry of epilepsy. Springfield 111.: Thomas (1960).Google Scholar
  65. Vrba, R., “Glucose metabolism in rat brain in vivo.” Nature (London). 195:663–65 (1962).PubMedCrossRefGoogle Scholar
  66. Waddell, W. J., and Butler, T. C., “Calculation of intracellular from the distribution of 5.5-dimethyl-2.4-oxazolidinedione (DMO). Application to skeletal muscle of the dog.” J. Clin. Invest. 38:720–29 (1959).PubMedCrossRefGoogle Scholar
  67. Waddell, W. J., and Butler, T. C., “Intracellular.” Physiol. Rev. 49:285–329 (1969).PubMedGoogle Scholar
  68. Waelsch, H., Berl, S., Rossi, C. A., Clarke, D. D., and Purpura, D. P., “Quantitative aspects of CO2 fixation in mammalian brain in vivo.” J. Neurochem. 11:717–28 (1964).PubMedCrossRefGoogle Scholar
  69. Wallace, W. M., and Hastings, A. B., “The distribution of the bicarbonate ion in mammalian muscle.” Biol. Chem. 144: 637–49 (1942).Google Scholar
  70. Weyne, J., and Leusen, I., “Bicarbonate, chloride and lactate in brain during acid-base alterations.” In Ion homeostasis of the brain. B. K. Siesjö and S. C. Sørensen, eds. Copenhagen: Munksgaard (1971).Google Scholar
  71. Williamson, D. H., Lund, P., and Krebs, H. A., “The redox state of free nicotinamideadenine dinucleotide in the cytoplasm and mitochondria of rat liver.” Biochem. J. 103:514–27 (1967).PubMedGoogle Scholar
  72. Woodbury, D. M., and Karler, R., “The role of carbon dioxide in the nervous system.” Anesthesiology. 21:686–703 (1960).PubMedCrossRefGoogle Scholar
  73. Woodward, D. L., Reed, D. J., and Woodbury, D. M., “Extracellular space of rat cerebral cortex.” Am. J. Physiol. 212:367–70 (1967).PubMedGoogle Scholar
  74. Wyke, B., Brain function and metabolic disorders. London: Butterworths (1963).Google Scholar

Bibliography

  1. Cameron, I. R., Davson, H., and Segal, M. B., “The effect of hypercapnia on the blood- brain barrier permeability to sucrose in the rabbit.” Yale J. Biol Med. 42:241–47 (1970).Google Scholar
  2. Ponten, U., and Siesjö, B. K., “Gradients of CO2 tension in the brain.” Acta Physiol Scand. 67:129–40(1966).PubMedCrossRefGoogle Scholar
  3. Siesjö, B., and Thews, G., “Ein Verfahren zur Bestimmung der CO2-leitfähigkeit, der CO2-diffusionskoeffizienten und des scheinbaren CO22-löslichkeitskoefficienten im Gehirngewebe.” Pflüg. Arch. 276:192–210 (1962).CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1974

Authors and Affiliations

  • Bo K. Siesjö
    • 1
  • Jaroslava Folbergrová
    • 1
  • Kenneth Messeter
    • 1
  1. 1.The Brain Research LaboratoryE-Blocket, University HospitalLundSweden

Personalised recommendations