The Transport of Metabolizable Substances into the Living Brain

  • O. E. Pratt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 69)


Much knowledge about the many enzymic processes by which the cerebral cells can change one substance into another has been derived from in vitro work. However, such in vitro experiments do not tell us the quantities of the various nutrient substances that the living brain needs to obtain from the blood in order to function normally. Nor do they tell us about the direction in which the various metabolic pathways act in life. In order to discover the needs of the cerebral tissues for metabolizable substances the quantities that enter and leave the brain during life must be studied. Over the last decade advances in technique in the in vivo field have enabled the study of various aspects of cerebral metabolism to be carried out with greater accuracy than has been possible in the past. For example, advances have been made in the following fields: the rates at which substances enter the brain; the factors which interfere with the entry of these substances; the conditions under which supply becomes inadequate to meet fully the metabolic needs of the brain and how far the brain, when deprived of normal substrate, can make good the deficiency by metabolizing an alternative substance. From these advances a common pattern emerges — that transport processes are of great importance in controlling the levels of metabolites in the brain.43


Aromatic Amino Acid Amino Acid Transport Ketone Body Branch Chain Amino Acid Neutral Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Andrews, T.M., and Tata, J.R., Protein synthesis by membrane- bound and free ribosomes of the developing rat cerebral cortex. Biochemical Journal, 124 (1971) 883–889.CrossRefGoogle Scholar
  2. 2.
    Bachelard, H.S., Daniel, P.M., Love, E.R., and Pratt, O.E., The transport of glucose into the brain of the rat in vivo. Proceedings of the Royal Society, London, B., 183 (1973) 71–82.ADSCrossRefGoogle Scholar
  3. 3.
    Balazs, R., Control of glutamate metabolism. The effect of pyruvate. Journal of Neurochemistry, 12 (1965) 63–76.CrossRefGoogle Scholar
  4. 4.
    Baños, G., Daniel, P.M., Moorhouse, S.R., and Pratt O.E., The passage of amino acids into the rat’s brain. Journal of Physiology, 210 (1970) 149P.Google Scholar
  5. 5.
    Baños, G., Daniel, P.M., Moorhouse, S.R., and Pratt, O.E., The entry of amino acids into the brain of the rat during the postnatal period. Journal of Physiology, 213 (1971) 45–46P.Google Scholar
  6. 6.
    Baños, G., Daniel, P.M., Moorhouse, S.R., and Pratt, O.E., The influx of amino acids into the brain of the rat in vivo: the essential compared with some non-essential amino acids. Proceedings of the Royal Society, London, B., 183 (1973) 59–70.ADSCrossRefGoogle Scholar
  7. 7.
    Baños, G., Daniel, P.M., Moorhouse, S.R. and Pratt, O.E.,, Inhibition of entry of some amino acids into the brain, with observations on mental retardation in the aminoacidurias. Psychological Medicine, 4 (1974) 262–269.CrossRefGoogle Scholar
  8. 8.
    Baños, G., Daniel, P.M., Moorhouse, S.R., and Pratt, O.E., The requirements of the brain for some amino acids. Journal of Physiology, 246 (1975) 539–548.CrossRefGoogle Scholar
  9. 9.
    Baños, G., Daniel, P.M., Moorhouse, S.R., Pratt, O.E., and Wilson, P., Inhibition of neutral amino acid entry into the brain of the rat in vivo. Journal of Physiology, 237 (1974) 22–23P.Google Scholar
  10. 10.
    Baiios, G., Daniel, P.M., and Pratt, O.E., Inhibition of entry of L-arginine into the brain of the rat, in vivo, by L-lysine or L-ornithine. Journal of Physiology, 214 (1971) 24–25P.Google Scholar
  11. 11.
    Baños, G., Daniel, P.M., and Pratt, O.E., Saturation of a shared mechanism which transports L-arginine and L-lysine into the brain of the living rat. Journal of Physiology, 236 (1974) 29–41.CrossRefGoogle Scholar
  12. 12.
    Battistin, L., Grynbaum, A., and Lajtha, A., The uptake of various amino acids by the mouse brain in vivo. Brain Research, 29 (1971) 85–99.CrossRefGoogle Scholar
  13. 13.
    Blasberg, R., and Lajtha, A., Substrate specificity of steady state amino acid transport in mouse brain slices. Archives of biochemistry and biophysics, 112 (1965) 361–377.CrossRefGoogle Scholar
  14. 14.
    Carlsson, A., The in vivo estimation of rates of tryptophan and tyrosine hydroxylation: effects of alterations in enz3mie environment and neuronal activity. In G.E.W. Wolstenholme and D.W. Fitzsimons (Eds.) Aromatic amino acids in the brain, Ciba Foundation Symposium (new series), Elsevier, Amsterdam, 1974, pp. 117–125.Google Scholar
  15. 15.
    Christensen, H.N., de Cespedes, C., Handlogten, M.E., and Ronquist, G., Energisation of amino acid transport, studied for the Ehrlich ascites tumour cell. Biochimica biophysica Acta, 300 (1973) 487–522.CrossRefGoogle Scholar
  16. 16.
    Cohen, S.R., and Lajtha, A., Amino acid transport. In A. Lajtha (Ed.), Handbook of Neurochemistry, Plenum Press, New York, London, 1972, vol. 7, pp. 543–572.CrossRefGoogle Scholar
  17. 17.
    Crockett, M.E., Daniel, P.M., and Pratt, O.E., Saturation of shared mechanisms transporting some neutral amino acids into the brain. (1976) in preparation.Google Scholar
  18. 18.
    Crone, C., Facilitated transfer of glucose from the blood into brain tissue. Journal of Physiology, 181 (1965) 103–113.CrossRefGoogle Scholar
  19. 19.
    Crone, C., and Thompson, A.M., Permeability of brain capillaries. In C. Crone and N.A. Lassen (Eds.), Capillary permeability, Munksgaard, Copenhagen, 1970, pp. 447–453.Google Scholar
  20. 19a.
    Curtis, D.R., and Johnston, G.A.R., Amino acid transmitters in the mammalian central nervous system. In R.H. Adrian et al. (Eds.), Ergebnisse der Physiologie (Reviews of Physiology), Springer-Verlag Berlin, Heidelberg, New York, 1974, pp. 97–188.Google Scholar
  21. 20.
    Curzon, G., Knott, P.J., Murray-Lyon, I.M., Record, C.O., and Williams, R., Disturbed brain tryptophan metabolism in hepatic coma. Lancet, i (1975) 1092–1093.CrossRefGoogle Scholar
  22. 21.
    Daniel, P.M., Donaldson, J., and Pratt, O.E., The rapid achievement and maintenance of a steady level of an injected substance in the blood plasma. Journal of Physiology, 237 (1974) 8–9P.Google Scholar
  23. 22.
    Daniel, P.M., Donaldson, J., and Pratt, O.E., A method for injecting substances into the circulation to reach rapidly and to maintain a steady level. Medical and Biological Engineering, 13 (1975) 214–227.CrossRefGoogle Scholar
  24. 23.
    Daniel, P.M., Love, E.R., Moorhouse, S.R., and Pratt, O.E., Amino acids, insulin and hepatic coma. Lancet, ii (1975) 179–180.CrossRefGoogle Scholar
  25. 24.
    Daniel, P.M., Love, E.R., Moorhouse, S.R., and Pratt, O.E., The role of the extracellular space in the transport of substances into the brain (1976) in preparation.Google Scholar
  26. 25.
    Daniel, P.M., Love, E.R., Moorhouse, S.R., Pratt, O.E., and Wilson, P., Factors influencing utilisation of ketone-bodies by brain in normal rats and rats with ketoacidosis. Lancet, ii (1971) 637–638.CrossRefGoogle Scholar
  27. 26.
    Daniel, P.M., Love, E.R., Moorhouse, S.R., Pratt, O.E., and Wilson, P. The movement of ketone bodies, glucose, pyruvate and lactate between the blood and the brain of rats. Journal of Physiology, 221 (1972) 22–23P.Google Scholar
  28. 27.
    Daniel, P.M., Love, E.R., Moorhouse, S.R., Pratt, O.E., and Wilson, P. A method for rapidly washing the blood out of an organ or tissue of the anaesthetized living animal. Journal of Physiology, 237 (1974) 11–12P.Google Scholar
  29. 28.
    Daniel, P.M., Love, E.R., and Pratt, O.E., Insulin and the way the brain handles glucose. Journal of Neurochemistry, 25 (1975) 471–476.CrossRefGoogle Scholar
  30. 29.
    Daniel, P.M., Love, E.R., and Pratt, O.E., The effect of insulin upon the cerebral metabolism of glucose in prolonged hyper- glycaemia. (1976) in preparation.Google Scholar
  31. 30.
    Daniel, P.M., Love, E.R., and Pratt, O.E., Hypothyroidism and aminoacid entry into brain and muscle. Lancet, ii (1975) 872.CrossRefGoogle Scholar
  32. 31.
    Daniel, P.M., Moorhouse, S.R., and Pratt, O.E., Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain. Psychological Medicine,(1976) in the press.Google Scholar
  33. 32.
    Daniel, P.M., Pratt, O.E., and Wilson, P., Partial exclusion of an essential amino acid from the brain: competitive inhibition of the transport of L-leucine into the brain by raised L-valine in the circulation. (1976) in preparation.Google Scholar
  34. 33.
    Dobbing, J., The later development of the central nervous system and its vulnerability. In J.A. Davis and J. Dobbing (Eds.), Scientific Foundations of Paediatrics. Heinemann, London, 1974, pp. 565–577.Google Scholar
  35. 34.
    Fisch, R.O., and Anderson, J.A., Maternal phenylketonuria. In H. Eickel, F.P. Hudson and L.I. Woolf (Eds.), Phenylketonuria and some other inborn errors of amino acid metabolism. Thieme, Stuttgart, 1971, pp. 73–80.Google Scholar
  36. 35.
    Gaitonde, M.K., Dahl, D.R., and Elliott, K.A.C., Entry of glucose carbon into amino acids of rat brain and liver in vivo after injection of uniformly 14C-labelled glucose. Biochemical Journal, 94 (1965) 345–352.CrossRefGoogle Scholar
  37. 36.
    Gal, E.M., Armstrong, J.C., and Ginsberg, B., The nature of in vitro hydroxylation of L-tryptophan by brain tissue. Journal of Neurochemistry, 13 (1966) 643–654.CrossRefGoogle Scholar
  38. 37.
    Geel, S.E., Valcana, T.,and Timaras, P.S., The effect of neonatal hypothyroidism and of thyroxine on L-14C leucine incorporation in protein in vivo and the relationship to ionic levels in the developing brain. Brain Research, 4 (1967) 143–150.CrossRefGoogle Scholar
  39. 38.
    Gilboe, D.D., and Betz, A.L., Kinetics of glucose transport in the isolated dog brain. American Journal of Physiology, 219 (1970) 774–778.CrossRefGoogle Scholar
  40. 39.
    Guroff, G., and Abramowitz, A., A simple radioisotope assay for phenylalanine hydroxylase. Analytical Biochemistry, 19 (1967) 548–555.CrossRefGoogle Scholar
  41. 40.
    Hawkins, R.A., Williamson, D.H., and Krebs, H.A., Ketone-body utilization by adult and suckling rat brain in vivo. Biochemical Journal, 122 (1971) 13–18.CrossRefGoogle Scholar
  42. 41.
    Hsia, Do Y-Y., Phenylketonuria and its variants. In A.G. Steinberg and A.G. Beam (Eds.), Progress in Medical Genetics, Heinemann, London, 1970, vol. 7. pp. 29–68.Google Scholar
  43. 42.
    Lajtha, A., Protein metabolism of the nervous system. International Review of Neurobiology, Academic Press, New York, London, 6 (1964) 1–98.Google Scholar
  44. 43.
    Lajtha, A., Transport as control mechanism of cerebral metabolite levels. In A. Lajtha and D.H. Ford (Eds.), Brain barrier systems. Progress in brain research. Elsevier, Amsterdam, 1968, vol. 29. pp. 201–216.CrossRefGoogle Scholar
  45. 44.
    Lajtha, A., Amino acid transport in the brain in vivo and in vitro. In G.E.W. Wolstenholme and D.Wo Fitzsimons (Eds.), Aromatic amino acids in the brain. Ciba Foundation Symposium 22 (new series), Elsevier, Amsterdam, 1974, pp. 25–410Google Scholar
  46. 45.
    Lassen, N.A., Cerebral blood flow and metabolism in health and disease. Research Publications, Association for Research in Nervous and Mental Disease, Williams and Wilkins, Baltimore, 41 (1966) 205–212.Google Scholar
  47. 46.
    Levin, B., Hereditary metabolic disorders of the urea cycle. In O. Bodansky and A.L. Latner (Eds.), Advances in Clinical Chemistry, Academic Press, New York, London, 1971, vol. 14, pp. 65–143.Google Scholar
  48. 47.
    Levin, V., and Patlak, C.S., A compartmental analysis of 24Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid. Journal of Physiology, 224 (1972) 559–581.CrossRefGoogle Scholar
  49. 48.
    Mcllwain, H., and Bachelard, H.S., Biochemistry of the central nervous system. Churchill, London, 1971, fourth edition.Google Scholar
  50. 49.
    Munro, H.N., Fernstrom, J.D., and Wurtman, R.J., Insulin, plasma aminoacid imbalance and hepatic coma, Lancet, i (1975) 722–724.CrossRefGoogle Scholar
  51. 50.
    Neame, K.D., Transport, metabolism and pharamcology of amino acids in brain. In A.N. Davison and J. Dobbing (Eds.), Applied Neurochemistry, Blackwell, Oxford, 1968, pp. 119–177.Google Scholar
  52. 51.
    Oldendorf, W.H., Brain uptake of radio-labelled amino acids, amines and hexoses after arterial injection. American Journal of Physiology, 221 (1971) 1629–1639.CrossRefGoogle Scholar
  53. 52.
    Owen, O.E., Morgan, A.P., Kemp, H.B., Sullivan, J.M., Herrera, M.G., and Cahill, G.F. Jr., Brain metabolism during fasting. Journal of Clinical Investigation, 46 (1967) 1589–1595.CrossRefGoogle Scholar
  54. 53.
    Pratt, O.E., An electronically controlled syringe drive for giving an injection at a variable rate according to a preset programme. Journal of Physiology, 237 (1974) 5–6P.Google Scholar
  55. 54.
    Seta, K., Sansur, M., and Lajtha, A., The rate of incorporation of amino acids into brain protein during infusion in the rat. Biochimica Biophysica Acta, 294 (1973) 472–480.CrossRefGoogle Scholar
  56. 55.
    Shank, R.P., and Aprison, M.H., The metabolism in vivo of glycine and serine in eight areas of the rat central nervous system. Journal of Neurochemistry, 17 (1970) 1461–1475.CrossRefGoogle Scholar
  57. 56.
    Stanbury, J.B., Wyngaarden, J.B., and Fredrickson, D.S., The metabolic basis of inherited disease, McGraw-Hill, New York, London, 1972, third edition.Google Scholar
  58. 57.
    Strecker, H.J., Biochemistry of selected amino acids. In A. Lajtha (Ed.), Handbook of Neurochemistry, Plenum Press, New York, London, 1970, vol. 3, pp. 173–207.Google Scholar
  59. 58.
    Yudilevich, D.L., and De Rose, N., Blood-brain transfer of glucose and other molecules measured by rapid indicator dilution. American Journal of Physiology, 220 (1971) 841–846.CrossRefGoogle Scholar
  60. 59.
    Yudilevich, D.L., De Rose, N., and Sepulveda, F.V., Facilitated transport of amino acids through the blood-brain barrier of the dog studied in a single capillary circulation. Brain Research, 44 (1972) 569–578.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • O. E. Pratt
    • 1
  1. 1.Department of NeuropathologyInstitute of PsychiatryLondonEngland

Personalised recommendations