Effect of Acute Hyperammonemia on Metabolism and Cerebral Energy State

  • Gianni Benzi
  • E. Arrigoni
  • R. F. Villa
  • A. Agnoli
Part of the Monographien aus dem Gesamtgebiete der Psychiatrie book series (PSYCHIATRIE, volume 18)

Abstract

The acute effect of hyperammonemia, kept at the level of 0.2 mM by adding ammonium acetate to circulating blood, was evaluated in the isolated dog brain in situ. The interference of the transmethylating system of S-adenosyl-L-methionine was also studied, by means of perfusions with S-adenosyl-L-methionine or adenosine (blood level 0.4 mM). The changes induced by the hyperammonemia syndrome on the glutamate-ammonia system (pyruvate, a-oxoglutarate, oxaloacetate, L-alanine, L-glutamate, L-aspartate, L-glutamine, NH 4 + ) were evaluated. The cerebral detoxication of ammonia is connected with the formation of glutamine and, to a lesser extent, of alanine, balanced by a decrease in aspartate; glutamate, oxaloacetate, pyruvate, and a-oxoglutarate are unmodified or slightly modified. This shows that the glutamate-ammonia system is an integrated biochemical system where NH 4 + represents the mobile element which modulates the interconversion of components.

Keywords

Lactate Alanine Methionine Bran Urethane 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Alleweis, C, Magnes, J.: The uptake and oxidation of glucose by the perfused cat brain. J. Neurochem. 2, 326–336 (1968)CrossRefGoogle Scholar
  2. 2.
    Benjamin, A.M., Quastel, J.H.: Locations of amino acids in brain slices from the rat. Tetrodotoxin-sensitive release of amino acids. Biochem. J. 128, 631–646 (1972)PubMedGoogle Scholar
  3. 3.
    Benjamin, A.M., Quastel, J.H.: Metabolism of amino acids and ammonia in rat brain cortex slices in vitro: a possible role of ammonia in brain function. J. Neurochem. 25, 197–206 (1975)PubMedCrossRefGoogle Scholar
  4. 4.
    Benzi, G., Berte’, F., Arrigoni, E., Manzo, L.: Study of the cerebral metabolizing activity in the newborn dog utilizing the isolated perfused brain in situ technique. J. pharm. Sci. 58, 885–887 (1969)PubMedCrossRefGoogle Scholar
  5. 5.
    Benzi, G., Berte’, F., Crema, A., Frigo, G.M.: Cerebral drug metabolism investigated by isolated perfused brain in situ. J. pharm. Sci. 56, 1349–1351 (1967)PubMedCrossRefGoogle Scholar
  6. 6.
    Benzi, G., De Bernardi, M., Manzo, L., Ferrara, A., Panceri, P., Arrigoni, E., Berte’, F.: Effect of lysergide and nimergoline on glucose metabolism investigated on the dog brain isolated in situ. J. pharm. Sci. 61, 348–352 (1972)PubMedCrossRefGoogle Scholar
  7. 7.
    Benzi, G., Manzo, L., De Bernardi, M., Ferrara, A., Sanguinetti, L., Arrigoni, E., Berte’, F.: Action of lysergide, ephedrine, and nimergoline on brain metabolizing activity, J. pharm. Sci. 60, 1320–1324 (1971)PubMedCrossRefGoogle Scholar
  8. 8.
    Bergmeyer, H.U., Bernt, E.: 2-Oxoglutarate. UV spectrophotometry determination. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. III, 1577–1580Google Scholar
  9. 9.
    Bergmeyer, H.U., Bernt, E., Möllering, H., Pfleiderer, G.: L-aspartate and L-aspar-agine. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. IV, pp. 1696–1700CrossRefGoogle Scholar
  10. 10.
    Bergmeyer, H.U., Bernt, E., Schmidt, F., Stork, H.: D-Glucose. Determination with hexokinase and glucose-6-phosphate dehydrogenase. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English Edition, 1974, Vol. III, pp. 1196–1201Google Scholar
  11. 11.
    Berl, S., Takagaki, G., Clarke, D.D., Waelsch, H.: Carbon dioxide fixation in the brain. J. biol. Chem. 237, 2570–2573 (1962)PubMedGoogle Scholar
  12. 12.
    Beutler, H.O., Michal, G.: L-Glutamate. Determination with glutamate dehydrogenase diaphorase, and tetrazolium salts. In: Methods of Enzymatic Analysis Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. IV, pp. 1708–1713Google Scholar
  13. 13.
    Cantoni, G.L.: S-adenosyl-L-methionine; a new intermediate formed enzymatically from L-methionine and adenosinetriphosphate. J. biol. Chem. 204, 403–410 (1953)Google Scholar
  14. 14.
    Czok, R., Lamprecht, W.: Pyruvate, phosphoenolpyruvate and D-glycerate-2-phos-phate. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. III, pp. 1446–1451Google Scholar
  15. 15.
    Faulconer, A., Jr.: Correlation of concentrations of ether in arterial blood with elec-tro-encephalographic patterns occuring during ether-oxygen and during nitrous oxide, oxygen and ether anesthesia of human surgical patients. Anesthesiology 13, 361–366 (1952)PubMedCrossRefGoogle Scholar
  16. 16.
    Geiger, A.: Correlation of brain metabolism and function by the use of a brain perfusion method in situ. Physiol. Rev. 38, 1–20 (1958)PubMedGoogle Scholar
  17. 17.
    Geiger, A., Magnes, J.: The isolation of the cerebral circulation and the perfusion of the brain in the living cat. Amer. J. Physiol. 149, 517–537 (1947)PubMedGoogle Scholar
  18. 18.
    Geiger, A., Magnes, J., Taylor, R.M., Veralli, M.: Effect of blood constituents on uptake of glucose and on metabolic rate of the brain in perfusion experiments. Amer. J.Physiol. 177, 138–149 (1954)PubMedGoogle Scholar
  19. 19.
    Gilboe, D.D., Betz, A.L.: Kinetics of glucose transport in the isolated dog brain. Amer. J. Physiol. 219, 774–778 (1970)PubMedGoogle Scholar
  20. 20.
    Gilboe, D.D., Betz, A.L.: Oxygen uptake in the isolated canine brain. Amer. J. Physiol. 224, 588–595 (1973)PubMedGoogle Scholar
  21. 21.
    Gilboe, D.D., Andrews, R.L., Dardenne, G.: Factors affecting glucose uptake by the isolated dog brain. Amer. J. Physiol. 219, 767–773 (1970)PubMedGoogle Scholar
  22. 22.
    Gilboe, D.D., Betz, L.A., Langebartel, D.A.: A guide for the isolation of the canine brain. J. appl. Physiol. 34, 534–537 (1973)PubMedGoogle Scholar
  23. 23.
    Gilboe, D.D., Cotanch, W.W., Glover, M.B.: Isolation and mechanical maintenace of the dog brain. Nature (Lond.) 206, 94–96 (1965)CrossRefGoogle Scholar
  24. 24.
    Gilboe, D.D., Cotanch, W.W., Glover, M.B., Levin, V.A.: Changes in electrolytes, pH, and pressure of blood perfusing isolated dog brain. Amer. J. Physiol. 212, 589–594 (1967)PubMedGoogle Scholar
  25. 25.
    Gilboe, D.D., Morris, B.G., Cotanch, W.W.: Blood filtration and its effect on glucose metabolism by the isolated dog brain. Amer. J. Physiol. 213, 11–15 (1967)PubMedGoogle Scholar
  26. 26.
    Grassl, M.: L-Alanine. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. IV, pp. 1682–1685Google Scholar
  27. 27.
    Greenberg, D.M.: Biological Methylation. Advanc. Enzymol. 25, 395–431 (1963)Google Scholar
  28. 28.
    Gutmann, I., Wahlefeld, A.W.: L-Lactate. Determination with lactate dehydrogenase and NAD. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. III, pp. 1464–1468Google Scholar
  29. 29.
    Hawkins, R.A., Miller, A.L., Nielsen, R.C., Veech, R.L.: The acute action of ammonia on rat brain metabolism “in vivo”. Biochem. J. 134, 1001–1008 (1973)PubMedGoogle Scholar
  30. 30.
    Hindfelt, B., Siesjo, B.K.: Cerebral effects of acute ammonia intoxication. The effect upon energy metabolism. Scand. J. clin. Lab. Invest. 28, 365–374 (1971)PubMedCrossRefGoogle Scholar
  31. 31.
    Krieglstein, J., Stock, R.: Comparative study of the effects of chloral hydrate and trichloroethanol on cerebral metabolism. Naunyn-Schmiedebergs Arch. Pharmacol. 277, 323–332.(1973)PubMedCrossRefGoogle Scholar
  32. 32.
    Kun, E., Kearney, E.B.: Ammonia. In: Methods of Enzymatic Analysis. Bergmeyer , H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. IV, pp. 1802–1806CrossRefGoogle Scholar
  33. 33.
    Lombardini, J.B., Talalay, P.: Formation, functions and regulatory importance of S-adenosyl-L-methionine. Advanc. Enzyme Regul. 9, 349–384 (1971)CrossRefGoogle Scholar
  34. 34.
    Lowry, O.H., Passonneau, J.V.: A Flexible System of Enzymatic Analysis. New York: Academic Press 1972, pp. 189–193Google Scholar
  35. 35.
    Lund, P.: L-Glutamine. Determination with glutaminase and glutamate dehydrogenase. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. IV, pp. 1719–1722Google Scholar
  36. 36.
    Möellering, H.: L-Malate. Determination with malate dehydrogenase and glutamate-oxaloacetate transaminase. In: Methods of Enzymatic Analysis. Bergmeyer, H.U. (ed.) New York-London: Academic Press. Second English edition, 1974, Vol. III, pp. 1589–1593Google Scholar
  37. 37.
    Möellering, H., Gruber, W.: Determination of citrate with citrate lyase. Analyt. Biochem. 17, 369–376 (1966)PubMedCrossRefGoogle Scholar
  38. 38.
    Neidle, A., Berg, C.J., van den, Grynbaum, A.: The heterogeneity of rat brain mitochondria on continuous sucrose gradients. J. Neurochem. 16, 225–234 (1969)PubMedCrossRefGoogle Scholar
  39. 39.
    Nilsson, L., Siesjö, B.K.: The effect of anesthetics upon labile phosphates and upon extra- and intracellular lactate, pyruvate and bicarbonate concentrations in the rat brain. Acta physiol. scand. 80, 235–248 (1970)PubMedCrossRefGoogle Scholar
  40. 40.
    Reijnierse, G.L.A., Veldstra, H., Berg, C.J., van den: Subcellular localization of y-aminobutyrate transaminase and glutamate dehydrogenase in adult rat brain. Biochem. J. 152, 469–475 (1975)PubMedGoogle Scholar
  41. 41.
    Salganicoff, L., De Robertis, E.: Subcellular distribution of the enzymes of the glutamic acid, glutamine and 7-aminobutyric acid cycles in rat brain. J. Nuerochem. 12, 287–309 (1965)CrossRefGoogle Scholar
  42. 42.
    Slyke, D.D. van, Neil, J.M.: The determination of gases in blood and other solutions by vacuum extraction and manometric measurements. I. J. biol. Chem. 61, 523–573 (1924)Google Scholar
  43. 43.
    Veech, R.L., Harris, R.L., Veloso, D., Veech, E.H.: Freeze-blowing: a new technique for the study of brain in vivo. J. Neurochem. 20, 183–188 (1973)PubMedCrossRefGoogle Scholar
  44. 44.
    Waelsch, H., Berl, S., Rossi, CA., Clarke, D.D., Purpura, D.P.: Quantitative aspects of CO2 fixation in mammalian brain “in vivo”. J. Neurochem. 11, 717–728 (1964)PubMedCrossRefGoogle Scholar
  45. 45.
    White R.J., Albin, M.S., Verdura, J.: Isolation of the monkey brain: in vitro preparation and maintenance. Science 141, 1060–1061 (1963)PubMedCrossRefGoogle Scholar
  46. 46.
    Williamson, D.H., Lund, P., Krebs, H.A.: The redox state of free nicotinamideadenine dinueleotide in the cytoplasm and mitochondria of rat liver. Biochem. J. 103, 514–527 (1967)PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1978

Authors and Affiliations

  • Gianni Benzi
    • 1
    • 2
  • E. Arrigoni
    • 1
    • 2
  • R. F. Villa
    • 1
    • 2
  • A. Agnoli
    • 1
    • 2
  1. 1.Department of PharmacologyUniversity of PaviaItaly
  2. 2.Department of Neurology and PsychiatryUniversity of L’AquilaItaly

Personalised recommendations