Kinetics of Tryptophan Transport Across the Blood-Brain Barrier

  • O. E. Pratt
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 15)


The transport of tryptophan across the blood-brain barrier in vivo has been analyzed kinetically to assess the influence upon it not only of the concentration of tryptophan in the blood plasma, but also of the inhibitory effect of fourteen other amino acids normally present in the circulation. The transport of tryptophan into the brain conforms to the equations of enzyme kinetics with competitive inhibition, provided appropriate modifications are made to take account of a non-saturable component (possibly passive diffusion) in the transport, and of the normal presence in the blood of other amino acids which act as competitive inhibitors. The inhibitor constant has been evaluated for each amino acid and in many cases it corresponds fairly closely with the Michaelis saturation constant for that amino acid, suggesting that tryptophan and these inhibitors share a common transport carrier. The implications of the kinetic analysis are considered for hormonal and metabolic disturbances which change the proportions of amino acids in the blood. The effect of an increase in competitive inhibition due to raised levels of amino acids is to make the tryptophan influx more directly dependent upon the level of tryptophan in the blood.


Aromatic Amino Acid Inhibitor Constant Neutral Amino Acid Tryptophan Concentration Free Tryptophan 
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. Baños, G., Daniel, P. M., Pratt, O. E.: The effect of age upon the entry of some amino acids into the brain, and their incorporation into cerebral protein. Develop. Med. Child Neurol. 20, 335–346 (1978).PubMedCrossRefGoogle Scholar
  2. Crockett, M. E., Daniel, P. M., Pratt, O. E.: Interaction between methionine and the branched-chain amino acids in transport across the blood-brain barrier (submitted 1978).Google Scholar
  3. Curzon, G., Friedl, J., Knott, P. J.: The effects of fatty acids on the binding of tryptophan to plasma proteins. Nature 242, 198–200 (1973).PubMedCrossRefGoogle Scholar
  4. Daniel, P. M., Donaldson, J., Pratt, O. E.: The rapid achievement and maintenance of a steady level of an injected substance in the blood plasma. J. Physiol. (Lond). 237, 8–9p (1974).Google Scholar
  5. Daniel, P. M., Donaldson, J., Pratt, O. E.: A method for injecting substances into the circulation to reach rapidly and to maintain a steady level. Med. Biol. Engineering 13, 214–227 (1975).CrossRefGoogle Scholar
  6. Daniel, P. M., Donaldson, J., Pratt, O. E.: Infusion schedules for prescribed blood concentration time courses. J. appl. Physiol. 41, 608 (1976).PubMedGoogle Scholar
  7. Daniel, P. M., Love, E. R., Moorhouse, S. R., Pratt, O. E.: Effect of insulin upon levels of amino acids in the blood and upon the influx of tryptophan into the brain. J. Physiol. (Lond.) (in press, 1979).Google Scholar
  8. Daniel, P.M., Love, E. R., Moorhouse, S.R., Pratt, O.E., Wilson, P.: A method for rapidly washing the blood out of an organ or tissue of the anaesthetized living animal. J. Physiol. (Lond.) 237, 11–12p (1974).Google Scholar
  9. Daniel, P. M., Love, E. R., Pratt, O. E.: The effect of non-aromatic amino acids normally found in the blood upon the transport of tryptophan across the blood-brain barrier. Unpublished observations (1978).Google Scholar
  10. Daniel, P. M., Moorhouse, S. R., Pratt, O. E.: Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain. Psychological Med. 6, 277–286 (1976).CrossRefGoogle Scholar
  11. Daniel, P. M., Moorhouse, S. R., Pratt, O. E.: Partial exclusion of tryptophan from the brain due to saturation of the transport carrier. J. Physiol. (Lond.) 282, 9–10p (1978 a).Google Scholar
  12. Daniel, P. M., Moorhouse, S. R., Pratt, O. E.: Post-natal changes in the transport of aromatic amino acids into the brain. J. Physiol. (Lond.) (in press, 1978 b).Google Scholar
  13. Daniel, P. M., Moorhouse, S. R., Pratt, O. E.: The exclusion of L-tryptophan from the brain by raised levels of other aromatic amino acids in the circulation and a way in which this exclusion can be overcome. Submitted (1978 c).Google Scholar
  14. Daniel, P. M., Pratt, O. E., Wilson, P.A.: The transport of L-leucine into the brain of the rat in vivo: saturable and non-saturable components of influx. Proc. Roy. Soc. (Lond.) B 196, 333–346 (1977 a).Google Scholar
  15. Daniel, P. M., Pratt, O. E., Wilson, P. A.: The exclusion of L-isoleucine or of L-leucine from the brain of the rat, caused by raised levels of L-valine in the circulation, and the manner in which this exclusion can be partially overcome. J. neurol. Sci. 31, 421–431 (1977 b).PubMedCrossRefGoogle Scholar
  16. Daniel, P. M., Pratt, O. E., Wilson, P. A.: The influx of isoleucine into the cerebral hemispheres and cerebellum: carrier-mediated transport and diffusion. Quart. J. exp. Physiol. 62, 163–173 (1977 c).PubMedGoogle Scholar
  17. Dixon, M.: The determination of enzyme inhibitor constants. Biochem. J. 55, 170–171 (1953).PubMedGoogle Scholar
  18. Dixon, M., Webb, E. C.: Enzymes, 2nd ed., pp. 318–320. London: Longmans. 1964.Google Scholar
  19. Donaldson, J., Pratt, O. E.: A method for displaying the effect of altering the constants of a function and an application to the problem of maintaining steady blood concentrations. J. Physiol. (Lond.) 252, 5–6p (1975).Google Scholar
  20. Fernando, J. C. R., Knott, P. J., Curzon, G.: The relevance of both plasma free tryptophan and insulin to rat brain tryptophan concentration. J. Neurochem. 27, 343–345 (1976).PubMedCrossRefGoogle Scholar
  21. Fernstrom, J. D., Hirsch, M. J., Faller, D. V.: Tryptophan concentrations in rat brain. Biochem. J. 160, 589–595 (1976).PubMedGoogle Scholar
  22. Fernstrom, J. D., Larin, F., Wurtman, R. J.: Correlation between brain tryptophan and plasma neutral amino acid levels following food conversion in rats. Life Sci. 13, 517–524 (1973).CrossRefGoogle Scholar
  23. Fernstrom, J. D., Wurtman, R. J.: Brain serotonin content-physiological regulation by plasma neutral amino acids. Science 178, 414–416 (1972).PubMedCrossRefGoogle Scholar
  24. Hunter, A., Downs, C. E.: The inhibition of arginase by amino acids. J. biol. Chem. 157, 427–446 (1945).Google Scholar
  25. Mood, A. M., Graybill, F. A.: Introduction to the theory of statistics, 2nd ed., pp. 152–164. New York: McGraw-Hill. 1963.Google Scholar
  26. Pardridge, W. M.: Regulation of amino acid availability to the brain. In: Nutrition and the Brain (Wurtman, R. J., Wurtman, J. J., eds.), Vol. 1. New York: Raven Press. 1977.Google Scholar
  27. Pardridge, W. M., Oldendorf, W. H.: Kinetic analysis of blood-brain barrier transport of amino acids. Biochim. Biophys. Acta 401, 128–136 (1975).PubMedCrossRefGoogle Scholar
  28. Pratt, O. E.: An electronically controlled syringe drive for giving an injection at a variable rate according to a preset programme. J. Physiol. (Lond.) 237, 5–6p (1975).Google Scholar
  29. Pratt, O. E.: The transport of metabolizable substances into the living brain. In: Transport Phenomena in the Nervous System: Physiological and Pathological Aspects (Proc. Satellite Symp. Int. Congr. Neurochem., Padua, 1975), pp. 55–75p. New York-London: Plenum Press. 1976.CrossRefGoogle Scholar
  30. Pratt, O. E.: Adequate nutrition of the developing brain. In: Advances in Perinatal Neurology, Vol. 1 (Korobkin, R., Guilleminault, C., eds.). New York: Spectrum Publications. 1978, in press.Google Scholar
  31. Tagliamonte, A., de Montis, M. G., Olianas, M., Onali, P. L., Gessa, G. L.: Possible role of insulin in the transport of tyrosine and tryptophan from blood to brain. Adv. Exp. Med. Biol. 69, 89–94 (1976).PubMedCrossRefGoogle Scholar
  32. Wilkinson, G. N.: Statistical estimations in enzyme kinetics. Biochem. J. 80, 324–332 (1961).PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1979

Authors and Affiliations

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

Personalised recommendations