Feeding, Stress, Exercise and the Supply of Amino Acids to the Brain

  • G. Curzon
Part of the NATO ASI Series book series (volume 20)


This chapter concerns some effects of food deprivation, feeding and stress on brain amino acids. In particular, it concerns amino acids which are precursors of transmitter amines. In the past, most attention has been paid to two of these, tyrosine and tryptophan, which through the action of tyrosine hydroxylase and tryptophan hydroxylase respectively are converted to 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytryptophan by reactions which are rate-limiting for catecholamine and 5-hydroxytryptamine (5-HT) synthesis. Various classical precursor loading experiments suggest that brain tyrosine hydroxylase is close to saturation with its substrate and is therefore relatively insensitive to altered substrate availability but that tryptophan hydroxylase is about 50% saturated (1, 2) and therefore more sensitive. Less attention has been paid to the fact that histidine decarboxylase is normally far below saturation with its precursor amino acid (3) and thus the synthesis of histamine is far more responsive to changes of precursor availability than are the syntheses of 5-HT or the catecholamines.


Neutral Amino Acid Plasma Amino Acid Immobilization Stress Large Neutral Amino Acid Plasma Tryptophan 
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  1. 1).
    CARLSSON, A., LINDQVIST, M. (1978). Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino acids in rat brain. Naunyn Schmiedebergs Arch. Pharmacol. 303: 157–164.PubMedCrossRefGoogle Scholar
  2. 2).
    SVED, A. F. (1983). Precursor control of the function of monoaminergic neurones. In: Nutrition and the Brain ( Wurtman, R. J., Wurtman, J. J., eds.), vol. 6, pp. 224–263, Raven Press, New York.Google Scholar
  3. 3).
    PARDRIDGE, W. M. (1986). Potential effects of the dipeptide sweetener aspartame on the brain. In: Nutrition and the Brain ( Wurtman, R. J., Wurtman, J. J., eds.), vol. 7, pp. 141–204, Raven Press, New York.Google Scholar
  4. 4).
    ENWONWU, C. 0. (1987). Differential effect of total food withdrawal and dietary protein restriction on brain content of free histidine in the rat. Neurochem. Res. 12: 483–487.PubMedCrossRefGoogle Scholar
  5. 5).
    KNOTT, P. J., JOSEPH, M. H., CURZON, G. (1973). Effects of food deprivation and immobilization on tryptophan and other amino acids in rat brain. J. Neurochem. 20: 249–251PubMedCrossRefGoogle Scholar
  6. 6).
    OLDENDORF, W. H., SZABO, J. (1976). Amino acid assignment to one of three blood-brain amino acid carriers. Am. J. Physiol. 230: 94–98.PubMedGoogle Scholar
  7. 7).
    PARDRIDGE, W. M. (1979). Kinetics of competitive inhibition of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 28: 103–118.CrossRefGoogle Scholar
  8. 8).
    CURZON, G., JOSEPH, M. H., KNOTT, P. J. (1972). Effects of immobilization and food deprivation on rat brain tryptophan metabolism. J. Neurochem. 19: 1969–1974.CrossRefGoogle Scholar
  9. 9).
    FERNSTROM, J. D., WURTMAN, R. J. (1971). Brain serotonin content: increase following ingestion of carbohydrate diet. Science 171: 1023–1025.CrossRefGoogle Scholar
  10. 10).
    SARNA, G. S., KANTAMANENI, B. D., CURZON, G. (1984). Variables influencing the effect of a meal on brain tryptophan. J. Neurochem. 44: 1575–1580.CrossRefGoogle Scholar
  11. 11).
    KNOTT, P. J., CURZON, G. (1972). Free tryptophan in plasma and brain tryptophan metabolism. Nature 239: 452–453.PubMedCrossRefGoogle Scholar
  12. 12).
    CURZON, G., FRIEDEL, J., KNOTT, P. J. (1973). The effects of fatty acids on the binding of tryptophan to plasma protein. Nature 242: 198–200.PubMedCrossRefGoogle Scholar
  13. 13).
    FERNSTROM, J. D., WURTMAN, R. J. (1973). Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178: 414–416.CrossRefGoogle Scholar
  14. 14).
    CURZON, G. (1979). Methodological problems in the determination of total and free plasma tryptophan. J. Neurol. Trans. SuppL 15: 221–226.Google Scholar
  15. 15).
    PEREZ-CRUET, J., CHASE, T. N., MURPHY, D. L. (1974). Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan and neutral amino acids in humans. Nature 248: 693–695.PubMedCrossRefGoogle Scholar
  16. 16).
    GILLMAN, P. K., BARTLETT, J R., BRIDGES, P. K., HUNT, A., PATEL, A. J., KANTAMANENI, B. D., CURZON, G. (1981). Indolic substances in plasma, cerebrospinal fluid and frontal cortex of human subjects infused with saline or tryptophan. J. Neurochem. 37: 410–417.PubMedCrossRefGoogle Scholar
  17. 17).
    FERNSTROM, J. D., LARIN, F., WURTMAN, R. J. (1973). Correlations between brain tryptophan and plasma neutral amino acid levels following food consumption in rats. Life Sci. 13: 517–524.CrossRefGoogle Scholar
  18. 18).
    CURZON, G. (1985). Effects of food intake on brain transmitter amine precursors and amine synthesis. In: Psychopharmacology and Food (Sandler, M., Silverstone, T.), pp. 59–70, Oxford.Google Scholar
  19. 19).
    MANS, A. M., BIEBUYCK, J. F., SAUNDERS, S. J., KIRSCH, R. E., HAWKINS, R. A. (1979). Tryptophan transport across the blood-brain barrier during acute hepatic failure. J. Neurochem. 33: 409–418.PubMedCrossRefGoogle Scholar
  20. 20).
    SCRIVER, C. R., GREGORY, D. M., SOVETTS, D., TISSENBAUM, G. (1985). Normal plasma free amino acid values in adults: the influence of some common physiological variables. Metabolism 34: 868–873.PubMedCrossRefGoogle Scholar
  21. 21).
    MILSON, J. P., MORGAN, M. Y., SHERLOCK, S. (1979). Factors affecting plasma amino acid concentrations in control subjects. Metabolism 28: 313–319.CrossRefGoogle Scholar
  22. 22).
    ASHLEY, D. V., BARCLAY, D. V., CHAUFFARD, F. A., MOENNOZ, D., LEATHWOOD, P. D. (1982). Plasma amino acid responses in humans to evening meals of differing nutritional composition. Am. J. Clin. Nutr. 36: 143–153.PubMedGoogle Scholar
  23. 23).
    ASHLEY, D. V. M., LIARDON, R., LEATHWOOD, P. D. (1985). Breakfast meal composition influences plasma tryptophan to large neutral amino acid ratios of healthy lean young men. J. Neural. Trans. 63: 271–283.CrossRefGoogle Scholar
  24. 24).
    LEATHWOOD, P. D. This volume.Google Scholar
  25. 25).
    MOLLER, S. E. (1985). Effect of various oral protein doses on plasma neutral amino acid levels. J. Neural. Trans. 61: 183–191.CrossRefGoogle Scholar
  26. 26).
    YOKOHOSHI, H., WURTMAN, R. J. (1986). Meal composition and plasma amino acid ratios: effect of various proteins or carbohydrates and of various protein concentrations. Metabolism 35: 837–842.CrossRefGoogle Scholar
  27. 27).
    GLAESER, B. S., MAHER, T. J., WURTMAN, R. J. (1983). Changes in brain levels of acidic, basic and neutral amino acids after consumption of single meals containing various proportions of protein. J. Neurochem. 41: 1016–1021PubMedCrossRefGoogle Scholar
  28. 28).
    BLOXAM, D. L., CURZON, G. (1978). A study of proposed determinants of brain tryptophan concentration in rats after portocaval anastomosis or sham operation. J. Neurochem. 31: 1255–1263.PubMedCrossRefGoogle Scholar
  29. 29).
    SARNA, G. S., TRICKLEBANK, M. D., KANTAMANENI, B. D., HUNT, A., PATEL, A. J., CURZON, G. (1982). Effect of age on variables influencing the supply of tryptophan to the brain. J. Neurochem. 39: 1283–1290.PubMedCrossRefGoogle Scholar
  30. 30).
    FERNSTROM, J. D., FERNSTROM, M. H., GRUBB, P. E. (1987). Twenty-four-hour variations in rat blood and brain levels of the aromatic and branched-chain amino acids: chronic effects of dietary protein content. Metabolism 36: 643–650.PubMedCrossRefGoogle Scholar
  31. 31).
    BLISS, E. L., AILION, J., ZWANZIGER, J. (1968). Metabolism of norepinephrine serotonin and dopamine in rat brain with stress. J. Pharm. Exp. Ther. 164: 122–134.Google Scholar
  32. 32).
    CURZON, G., KNOTT, P. J. (1974). Fatty acids and the disposition of tryptophan. In: Aromatic Amino Acids in the Brain (Ciba Foundation Symposium 22), pp. 217–229, Elsevier.Google Scholar
  33. 33).
    KENNETT, G. A., CURZON, G., HUNT, A., PATEL, A. J. (1986). Immobilization decreases amino acid concentrations in plasma but maintains or increases them in brain. J. Neurochem. 46: 208–212.PubMedCrossRefGoogle Scholar
  34. 34).
    MILAKOFSKY, L., HARE, T. A., MILLER, J. M., VOGEL, W. H. (1985). Rat plasma levels of amino acids and related compounds during stress. Life Sci. 36: 753–761PubMedCrossRefGoogle Scholar
  35. 35).
    HUTSON, P. H., KNOTT, P. J., CURZON, G. (1980). Effect of isoprenaline infusion on the distribution of tryptophan, tyrosine and isoleucine, between brain and other tissues. Biochem. Pharmac. 29: 509–516.CrossRefGoogle Scholar
  36. 36).
    SHAMOON, H., JACOB, R., SHERWIN, R. S. (1980). Epinephrine induced hypoaminoacidemia in normal and diabetic subjects: effects of blockade. Diabetes 11: 875–881CrossRefGoogle Scholar
  37. 37).
    PARDRIDGE, W. M. (1977). Regulation of amino acid availability to the brain. In: Nutrition and the Brain (Wurtman, R. J., Wurtman, J. J., eds.), vol. i, pp. 141–204. Raven Press, New York.Google Scholar
  38. 38).
    MANS, A. M., BIEBUYCK, J. F., DAVIS, D. W., HAWKINS, R. A. (1984). Portocaval anastomosis: brain and plasma metabolite abnormalities and the effect of nutritional therapy. J. Neurochem. 43: 697–705.PubMedCrossRefGoogle Scholar
  39. 39).
    BELOVA, T. I., JONSSON, G. (1982). Blood-brain barrier permeability and immobilization stress. Acta. Physiol. Scand. 116: 21–29.PubMedCrossRefGoogle Scholar
  40. 40).
    HAWKINS, R. A., MANS, A. M., BIEBUYCK, J. E. (1982). Amino acid supply to individual cerebral structures in awake and anaesthetized rats. Am. J. Physiol. 242: E1 - E11.PubMedGoogle Scholar
  41. 41).
    OHATA, M., FREDERICKS, W. R., SUNDARAM, V., RAPOPORT, S. I. (1981). Effect of immobilization stress on regional cerebral blood flow in the conscious rat. J. Cereb. Blood Flow Metab. 1: 187–194.PubMedCrossRefGoogle Scholar
  42. 42).
    LANGER, P., FOLDES, O., KVETNANSKY, L., CALMAN, J., TORDA, T., DAHER, F. (1983). Pituitary-thyroid function during acute immobilization stress in rats. Exp. Clin. Endocrinol. 82: 51–60.PubMedCrossRefGoogle Scholar
  43. 43).
    DANIEL, P. M., LOVE, E. R., PRATT, O. E. (1975). Hypothyroidism and amino acid entry into brain and muscle. Lancet 2: 872.PubMedCrossRefGoogle Scholar
  44. 44).
    ERIKSSON, T., CARLSSON, A. (1982). Isoprenaline increases brain concentrations of administered L-DOPA and L-tryptophan in the rat. Psychopharmacology (Berlin) 77: 98–100.CrossRefGoogle Scholar
  45. 45).
    KANT, G. J., LENOX, R. H., BUNNELL, B. N., MOUGEY, E. H., PENNINGTON, L. L., MEYERHOFF, J. L. (1983). Comparison of stress responses in male and female rats: pituitary cyclic AMP and plasma prolactic growth hormone and corticosterone. Psychoneuroendocrinology 8: 421–428.PubMedCrossRefGoogle Scholar
  46. 46).
    COCCHI, D., GIULIO, A., GROPPETTI, A., MANTEGAZZA, P., MULLER, E. E., SPANO, P. F. (1975). Hormonal imputs and brain tryptophan metabolism: the effect of growth hormone. Experientia 31: 384–385.PubMedCrossRefGoogle Scholar
  47. 47).
    TANG, L. C., COTZIAS, G. C. (1976). Modification of the actions of some neuroactive drugs by growth hormone. Arch. Neurol. 33: 131–134.PubMedGoogle Scholar
  48. 48).
    PARDRIDGE, W. M. (1979). Tryptophan transport through the blood-brain barrier: in vivo measurement of free and albumin-bound amino acid. Life Sci. 25: 1519–1528.PubMedCrossRefGoogle Scholar
  49. 49).
    KNOTT, P. J., HUTSON, P. H., CURZON, G. (1977). Fatty acid and tryptophan changes on disturbing groups of rats and caging them singly. PharmacoL Biochem. Behay. 7: 245–252.CrossRefGoogle Scholar
  50. 50).
    BANOS, G., DANIEL, R. M., MOORHOUSE, S. R., PRATT, O. E. (1974). Inhibition of entry of some amino acids into the brain with observations on mental retardation in the aminoacidurias. PsychoL Med. 4: 262–269.PubMedCrossRefGoogle Scholar
  51. 51).
    MARCOU, M., KENNETT, G. A., CURZON, G. (1987). Enhancement of brain dopamine metabolism by tyrosine during immobilization: an in vivo study using repeated cerebrospinal fluid sampling in conscious rats. J. Neurochem. 48: 1245–1251PubMedCrossRefGoogle Scholar
  52. 52).
    CHAOULOFF, F., ELGHOZI, J. L., GUEZENNEC, Y., LAUDE, D. (1985). Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-hydroxytryptamine metabolism of the rat. Br. J. Pharmacol. 86: 33–41.PubMedGoogle Scholar
  53. 53).
    CHAOULOFF, F., LAUDE, D., GUEZENNEC, Y., ELGHOZI, J. L. (1986). Motor activity increases tryptophan, 5-hydroxyindoleacetic acid and homovanillic acid in ventricular cerebrospinal fluid of the conscious rat. J. Neurochem. 46: 1313–1316.PubMedCrossRefGoogle Scholar
  54. 54).
    CHAOULOFF, F., KENNETT, G. A., SERRURRIER, B., MERINO, D., CURZON, G. (1986). Amino acid analysis demonstrates that increased plasma free tryptophan causes the increase of brain tryptophan during exercise in the rat. J. Neurochem. 46: 1647–1650.PubMedCrossRefGoogle Scholar
  55. 55).
    AHLBORG, G., FELIG, P., HAGENFELDT, L., HENDLER, R., WAHREN, J. (1974). Substrate turnover during prolonged exercise in man. J. Clin. Invest. 53: 1080–1090.PubMedCrossRefGoogle Scholar
  56. 56).
    FELIG, P., WAHREN, J. (1971). Amino acid metabolism in exercising man. J. Clin. Invest. 50: 2703–2714.PubMedCrossRefGoogle Scholar
  57. 57).
    MUTCH, B. J. C., BANISTER, E. W. (1983). Ammonia metabolism in exercise and fatigue: a review. Med. Sci. Sports. Exerc. 15: 41–50.PubMedGoogle Scholar
  58. 58).
    CHAOULOFF, F., LAUDE, D., MIGNOT, E., KAMOUN, P., ELGHOZI, J. L. (1985). Tryptophan and serotonin turnover rate in the brain of genetically hyperammonaemic mice. Neurochem. Int 7: 143–153.PubMedCrossRefGoogle Scholar
  59. 59).
    HAWKINS, R. A., MILLER, A. L., NIELSEN, R. C., VEECH, R. M. (1973). The acute action of ammonia in rat brain metabolism in vivo. Biochem. J. 134: 1001–1008.PubMedGoogle Scholar
  60. 60).
    RIGOTTI, P., JONUNG, T., PETERS, J. C., JAMES, J. H., FISCHER, R. E. (1985). Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of portocaval shunted rats. J. Neurochem. 44: 929–933.PubMedCrossRefGoogle Scholar
  61. 61).
    SWENSON, R. M., VOGEL, W. H. (1983). Plasma catecholamine and corticosterone as well as brain catecholamine changes during coping in rats exposed to stressful footshock. Pharmacol. Biochem. Behay. 18: 689–693.CrossRefGoogle Scholar
  62. 62).
    WEISS, J. M., GOODMAN, P. A., LOSITO, B. C., CORRIGAN, S., CHARRY, J. M., BAILEY, W. H. (1981). Behavioural depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Res. Rev. 3: 167–205.CrossRefGoogle Scholar
  63. 63).
    PETERS, J. C., HARPER, A. E. (1987). Acute effects of dietary proteins on food intake, tissue amino acids and brain serotonin. Am. J. PhysioL 252: R902 - R914.PubMedGoogle Scholar
  64. 64).
    FERNSTROM, J. D. (1987). Food induced changes in brain serotonin synthesis: is there a relationship to appetite for specific macronutrients? Appetite 8: 163–182.PubMedCrossRefGoogle Scholar
  65. 65).
    SUGRUE, M. F. (1987). Neuropharmacology of drugs affecting food intake. Pharmacol. Ther. 32: 145–182.PubMedCrossRefGoogle Scholar
  66. 66).
    KENNETT, G. A., DOURISH, C. T., CURZON, G. (1987). 5-HT1B; agonists induce anorexia at a post-synaptic site. Eur. J. Pharmacol. 141: 429–435.CrossRefGoogle Scholar
  67. 67).
    HUTSON, P. H., DOURISH, C. T., CURZON, G. (1988). Evidence that the hyperphagic response to 8-OH-DPAT is mediated by 5-HT1A receptors. Eur. J. Pharmacol. (in press).Google Scholar
  68. 68).
    HUTSON, R. H., SARNA, G. S., KANTAMANENI, B. D., CURZON, G. (1985). Monitoring the effect of a tryptophan load on brain indole metabolism in freely moving rats by simultaneous cerebrospinal fluid sampling and brain dialysis. J. Neurochem. 44: 1266–1273.PubMedCrossRefGoogle Scholar
  69. 69).
    SILVERSTONE, T., GOODALL, E. (1986). Serotonergic mechanisms in human feeding: the pharmacological evidence. Appetite (SuppL) 7: 85–97.Google Scholar
  70. 70).
    HRBOTICKY, N., LEITER, L. A., ANDERSON, G. H. (1985). Effects of L-tryptophan on short term food intake in lean men. Nutrition Res. 5: 595–607.CrossRefGoogle Scholar
  71. 71).
    JOSEPH, M. H., KENNETT, G. A. (1983). Corticosteroid response to stress depends upon increased tryptophan availability. Psychopharmacology 79: 79–81PubMedCrossRefGoogle Scholar
  72. 72).
    YEHUDA, R., MEYER, J. S. (1984). A role for serotonin in the hypothalamic-pituitary adrenal response to insulin stress. Neurochemistry 38: 25–32.Google Scholar
  73. 73).
    ALOI, J. A., INSEL, R. T., MUELLER, E. A., MURPHY, J. A. (1984). Neuroendocrine and behavioural effects of m-chlorophenylpiperazine administration in rhesus monkeys. Life Sci. 34: 1325–1331PubMedCrossRefGoogle Scholar
  74. 74).
    KOENIG, J. I., GUDELSKY, G. A., MELTZER, H. Y. (1987). Stimulation of corticosterone and B-endorphin secretion in the rat by selective 5-HT receptor subtype activation. Eur. J. Pharmacol. 137: 1–8.PubMedCrossRefGoogle Scholar
  75. 75).
    KELLY, S. J., FRANKLIN, K. B. J. (1984). Evidence that stress augments morphine analgesia by increasing brain tryptophan. Neurosci. Lett. 44: 305–310.PubMedCrossRefGoogle Scholar
  76. 76).
    RANSFORD, C. P. (1982). A role for amines in the antidepressant effect of exercise: a review. Med. Sci. Sports Exerc. 14: 1–10.PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • G. Curzon
    • 1
  1. 1.Department of NeurochemistryInstitute of NeurologyLondonUK

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