Serotonin pp 221-230 | Cite as

Tryptophan Availability and the Control of 5-Hydroxytryptamine and Tryptamine Synthesis in Human CNS

  • Simon N. Young
  • Serge Gauthier
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 133)


Administration of tryptophan to the rat results in an increased synthesis of 5-hydroxytryptamine (5HT) in the brain. (Ashcroft et al., 1965), because the rate-limiting enzyme in 5HT synthesis, tryptophan hydroxylase, is not normally saturated with tryptophan (Friedman et al., 1972). This is important physiologically as amounts of tryptophan as small as one twentieth of a rat’s normal daily intake can result in a significant rise of plasma and brain tryptophan and of brain 5HT (Fernstrom and Wurtman, 1971). In humans, as in rats, tryptophan administration will increase CNS 5HT synthesis (Eccleston et al.,1970). The fact that the level of a dietary component (tryptophan) can control the synthesis of a neurotransmitter (5HT) that is implicated in the control of various aspects of mood and the etiology of neuropsychiatric disorders is of obvious interest. Therefore we have attempted to gain more information on the role of tryptophan availability in controlling indoleamine synthesis and function in human CNS. The specific questions we have attempted to answer for humans are: (i) What is the relationship between plasma and brain tryptophan? (ii) Is control of the brain 5HT by tryptophan availability physiologically important? (iii) Is tryptophan availability important in controlling the synthesis of a related indoleamine, tryptamine? (iv) To what extent can tryptophan administration influence brain 5HT and tryptamine synthesis? (v) Can tryptophan administration influence indoleamine function as well as indoleamine synthesis?


Hepatic Encephalopathy Tryptophan Hydroxylase Hepatic Coma Large Neutral Amino Acid Plasma 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.


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  1. Anderson, G.M., and Purdy, W.C., 1979, A liquid chromatographicfluorimetric system for the analysis of indoles in physiological samples, Anal. Chem. 51:283.PubMedCrossRefGoogle Scholar
  2. Ashcroft, G.W., Eccleston, D., and Crawford, T.B.B., 1965, 5-Hydroxyindole metabolism in rat brain: a study of intermediate metabolism using the technique of tryptophan loading, J. Neurochem. 12:483.CrossRefGoogle Scholar
  3. Ashcroft, G.W., Crawford, T.B.B., Cundall, R.L., Davidson, D.L., Dobson, J., Dow, R.C., Eccleston, D., Loose, R.W., and Pullar, I.A., 1973, 5-Hydroxytryptamine metabolism in affective illness: the effect of tryptophan administration, Psychol. Med., 3: 326.PubMedCrossRefGoogle Scholar
  4. Chouinard, G., Young, S.N., Annable, L., Sourkes, T.L., and Kiriakos, R.Z., 1978, Tryptophan-nicotinamide combination in the treatment of newly admitted depressed patients, Commun. Psychopharmacol. 2:311.PubMedGoogle Scholar
  5. Chouinard, G., Young, S.N., Annable, L., and Sourkes, T.L., 1979, Tryptophan-nicotinamide, imipramine and their combination in depression, Acta Psychiat. Scand. 59:395.PubMedCrossRefGoogle Scholar
  6. Curzon, G., and Knott, P.J., 1974, Effects on plasma and brain tryptophan in the rat of drugs and hormones that influence the concentrations of unesterified fatty acid in the plasma, Brit. J. Pharmacol. 50:197.CrossRefGoogle Scholar
  7. Curzon, G., Kantamaneni, B.D., Bartlett, J.R., and Bridges, P.K., 1976, Transmitter precursors and metabolites in human ventricular cerebrospinal fluid. J. Neurochem. 26:613.PubMedCrossRefGoogle Scholar
  8. Denckla, W.D., and Dewey, H.K., 1967, The determination of tryptophan in plasma, liver, and urine, J. Lab. Clin. Med. 69:160.PubMedGoogle Scholar
  9. Ebert, M.H., and Perlow, M.J., 1977, Utility of cerebrospinal fluid measurements in studies of brain monoamines, in “Structure and Function of Monoamine Enzymes,” E. Usdin, N. Weiner and M.B.H. Youdim, eds., Marcel Dekker, Inc., New York.Google Scholar
  10. Eccleston, D., Ashcroft, G.W., Crawford, T.B.B., Stanton, J.B., Wood, D., and McTurk, P.H., 1970, Effect of tryptophan administration on 5HIAA in cerebrospinal fluid in man, J. Neurol. Neurosurg. Psychiat. 33:269.PubMedCrossRefGoogle Scholar
  11. Etienne, P., Young, S.N., and Sourkes, T.L., 1976, Inhibition by albumin of tryptophan uptake by rat brain, Nature 262: 144.Google Scholar
  12. Fernstrom, J.D., and Wurtman, R.J., 1971, Brain serotonin content: physiological dependence on plasma tryptophan levels, Science 173: 149.Google Scholar
  13. Fernstrom, J.D., 1977, Effects of the diet on brain neurotransmitters, Metabolism 26: 207.Google Scholar
  14. Friedman, P.A., Kappelman, A.H., and Kaufman, S., 1972, Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain, J. Biol. Chem. 247:4165.Google Scholar
  15. Garelis, E., Young, S.N., Lal, S., and Sourkes, T.L., 1974, Monoamine metabolites in lumbar CSF: the question of their origin in relation to clinical studies, Brain Res. 79: 1.PubMedCrossRefGoogle Scholar
  16. Gessa, G.L., and Tagliamonte, A., 1974, Possible role of free serum tryptophan in the control of brain tryptophan leveland serotonin synthesis, in: “Serotonin, New Vistas, Advances in Biochemical Psychopharmacology Vol. 11,”E. Costa, G.L. Gessa, and M. Sandler, eds., Raven Press, New York.Google Scholar
  17. Hartmann, E., 1977, L-Tryptophan: a rational hypnotic with clinical potential, Amer. J. Psychiat. 134:366.Google Scholar
  18. Ichiyama, A., Nakamura, S., Nishizuka, Y., and Hayaishi, 0., 1970, Enzymic studies on the biosynthesis of serotonin in mammalian brain, J. Biol. Chem. 245:1699.PubMedGoogle Scholar
  19. James, J.H., Escourrou, J., and Fischer, J.E., 1978, Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis, Science 200: 1395.Google Scholar
  20. Knell, A.J., Davidson, A.R., Williams, R., Kantamaneni, B.D., and Curzon, G., 1974, Dopamine and serotonin metabolism in hepatic encephalopathy, J. Brit. Med., i:549.Google Scholar
  21. Lal, S., Aronoff, A., Garelis, E., Sourkes, T.L., Young, S.N., and de la Vega, C.E., 1974, Cerebrospinal fluid, homovanillic acid, 5-hydroxyindoleacetic acid, lactic acid, and pH before and after probenecid in hepatic coma, Clin. Neurol. Neurosurg. 77:142.CrossRefGoogle Scholar
  22. Lal, S., Young, S.N., and Sourkes, T.L., 1975, 5-Hydroxytryptamine and hepatic coma, Lancet íi:979.CrossRefGoogle Scholar
  23. McMenamy, R.H., 1965, Binding of indole analogues to human serum albumin: effect of fatty acids, J. Biol. Chem. 240:4235.Google Scholar
  24. Oldendorf, W.H., and Szabo, J., 1976, Amino acid assignment to one of three blood-brain barrier amino acid carriers, Amer. J. Physiol. 230:94.Google Scholar
  25. Perez-Cruet, J., Chase, T.N., and Murphy, D.L., 1974, Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan and neutral amino acids in humans, Nature 248: 693.Google Scholar
  26. Philips, S.R., Durden, D.A., and Boulton, A.A., 1974,Identification and distribution of tryptamine in the rat, Can. J. Biochem. 52:447.Google Scholar
  27. Philips, S.R., Rozdilsky, B., and Boulton, A.A., 1978, Evidence for the presence of m-tyramine, p-tyramine, tryptamine, and phenylethylamine in the rat brain and several areas of the human brain, Biol. Psychiat. 13:51.Google Scholar
  28. Soeters, P.B., and Fischer, J.E., 1976, Insulin, glucagon, aminoacid imbalance, and hepatic encephalopathy, Lancet ii:880.Google Scholar
  29. Vapalahti, M., HyyppU, M., Nieminen, V., and Rinne, U.K., 1978, Brain monoamine metabolites and tryptophan in ventricular CSF of patients with spasm after aneurysm surgery, J. Neurosurg. 48: 58.Google Scholar
  30. Warsh, J.J., Coscina, D.V., Godse, D.D., and Chan, P.W., 1979, Dependence of brain tryptamine formation on tryptophan availability, J. Neurochem. 32:1191.PubMedCrossRefGoogle Scholar
  31. Young, S.N., Garelis, E., Lal, S., Martin, J.B., Molina-Negro, P., Ethier, R., and Sourkes, T.L., 1974, Tryptophan and 5-hydroxyindoleacetic acid in human cerebrospinal fluid,J. Neurochem., 22:777.PubMedCrossRefGoogle Scholar
  32. Young, S.N., Lal, S., Sourkes, T.L., Feldmuller, F., Aronoff, A., and Martin, J.B., 1975, Relationships between tryptophan in serum and CSF and 5-hydroxyindoleacetic acid in CSF of man: effect of cirrhosis of liver and probenecid administration, J. Neurol. Neurosurg. Psychiat. 38:322.CrossRefGoogle Scholar
  33. Young, S.N., Etienne, P., and Sourkes, T.L., 1976a, Relationship between rat brain and cisternal CSF tryptophan concentrations, J. Neurol. Neurosurg. Psychiat. 39:239.Google Scholar
  34. Young, S.N., Lal, S., Feldmuller, F., Sourkes, T.L., Ford, R.M., Kiely, M., and Martin, J.B., 1976b, Parallel variation of ventricular CSF tryptophan and free serum tryptophan in man, J. Neurol. Neurosurg. Psychiat. 39:61.Google Scholar
  35. Young, S.N., and Sourkes, T.L., 1977, Tryptophan in the central nervous system: regulation and significance, in:“Advances in Neurochemistry, Vol. 2,” B.W. Agranoff and M.H. Aprison, eds., Springer Science+Business Media New York.Google Scholar
  36. Young, S.N., Tsang, D., Lal, S., and Sourkes, T.L., 1977, Changes in the tryptophan content of excised human cerebral cortex, J. Neurochem. 28:439.Google Scholar
  37. Young, S.N., Anderson, G.M., Gauthier, S., and Purdy, W.C., 1979a, The origin of indoleacetic acid and indolepropionic acid in rat and human cerebrospinal fluid, J. Neurochem.,in press.Google Scholar
  38. Young, S.N., Gauthier, S., Anderson, G.M., and Purdy, W.C.,1979b, The significance of and relationships between major and minor tryptophan metabolites in cerebrospinal fluid, in : “Biological Psychiatry Today,” J. Obiols, C. Ballús, E. Gonzalez Monclûs and J. Pujol, eds.,Elsevier/North-Holland Biomedical Press, Amsterdam.Google Scholar
  39. Young, S.N., Anderson, G.M., and Purdy, W.C., 1980, Indoleamine metabolism in rat brain studied through measurements of tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in cerebrospinal fluid, J. Neurochem. in press.Google Scholar
  40. Yuwiler, A., Oldendorf, W.H., Geller, E., and Braun, L., 1977, Effect of albumin binding and amino acid competition on tryptophan uptake into brain, J. Neurochem. 28:1015.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Simon N. Young
    • 1
    • 2
  • Serge Gauthier
    • 1
    • 2
  1. 1.Department of PsychiatryMcGill UniversityMontrealCanada
  2. 2.Department of Neurology and NeurosurgeryMcGill UniversityCanada

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