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. 1976 Dec 15;160(3):589–595. doi: 10.1042/bj1600589

Tryptophan concentrations in rat brain. Failure to correlate with free serum tryptophan or its ratio to the sum of other serum neutral amino acids.

J D Fernstrom, M J Hirsch, D V Faller
PMCID: PMC1164274  PMID: 1016241

Abstract

Groups of rats were deprived of food overnight and then given free access to diets designed to raise (carbohydrate) or lower (carbohydrate and large neutral amino acids) brain tryptophan concentrations. Similar diets were supplemented with 40% fat and fed to other groups. All animals were killed 2h after food presentation. Sera from animals fed carbohydrate plus fat contained 2.5 times as much free tryptophan concentrations did not differ. Similarly, sera from rats fed on carbohydrate, large neutral amino acids, and 40% fat contained 5 times as much free tryptophan as those from rats given this meal without fat, but brain tryptophan concentrations increased by only 26%. Correlations were made between brain tryptophan and (1) free serum tryptophan, (2) the ratio of free serum tryptophan to the sum of the other large neutral amino acids in serum that compete with it for uptake into the brain, (3) total serum tryptophan or (4) the ratio of total serum tryptophan to the sum of its circulating competitors. The r values for correlations (3) and (4) (i.e. those involving total serum tryptophan) were appreciably higher than those for correlations (1) and (2). Brain tyrosine concentrations also were found to correlate well with the ratio of serum tyrosine to the sum of its competitors. Competition for uptake into the brain among large neutral amino acids (represented here by serum ratios) thus appears to determine the changes in the brain concentrations of these amino acids under physiological conditions(i.e. after food consumption). Total, not free, serum tryptophan is the relevant index for predicting brain tryptophan concentrations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Biggio G., Fadda F., Fanni P., Tagliamonte A., Gessa G. L. Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci. 1974 Apr 1;14(7):1321–1329. doi: 10.1016/0024-3205(74)90440-8. [DOI] [PubMed] [Google Scholar]
  2. Bloxam D. L., Warren W. H. Error in the determination of tryptophan by the method of Denkla and Dewey. A revised procedure. Anal Biochem. 1974 Aug;60(2):621–625. doi: 10.1016/0003-2697(74)90275-9. [DOI] [PubMed] [Google Scholar]
  3. Curzon G., Knott P. J. Effects on plasma and brain tryptophan in the rat of drugs and hormones that influence the concentration of unesterified fatty acid in the plasma. Br J Pharmacol. 1974 Feb;50(2):197–204. doi: 10.1111/j.1476-5381.1974.tb08562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Denckla W. D., Dewey H. K. The determination of tryptophan in plasma, liver, and urine. J Lab Clin Med. 1967 Jan;69(1):160–169. [PubMed] [Google Scholar]
  5. Fernstrom J. D., Faller D. V., Shabshelowitz H. Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing amino acids. J Neural Transm. 1975;36(2):113–121. doi: 10.1007/BF01256759. [DOI] [PubMed] [Google Scholar]
  6. Fernstrom J. D., Hirsch M. J., Madras B. K., Sudarsky L. Effects of skim milk, whole milk and light cream on serum tryptophan binding and brain tryptophan concentrations in rats. J Nutr. 1975 Oct;105(10):1359–1362. doi: 10.1093/jn/105.10.1359. [DOI] [PubMed] [Google Scholar]
  7. Fernstrom J. D., Wurtman R. J. Brain serotonin content: increase following ingestion of carbohydrate diet. Science. 1971 Dec 3;174(4013):1023–1025. doi: 10.1126/science.174.4013.1023. [DOI] [PubMed] [Google Scholar]
  8. Fernstrom J. D., Wurtman R. J. Brain serotonin content: physiological dependence on plasma tryptophan levels. Science. 1971 Jul 9;173(3992):149–152. doi: 10.1126/science.173.3992.149. [DOI] [PubMed] [Google Scholar]
  9. Fernstrom J. D., Wurtman R. J. Brain serotonin content: physiological regulation by plasma neutral amino acids. Science. 1972 Oct 27;178(4059):414–416. doi: 10.1126/science.178.4059.414. [DOI] [PubMed] [Google Scholar]
  10. GUROFF G., UDENFRIEND S. Studies on aromatic amino acid uptake by rat brain in vivo. Uptake of phenylalanine and of tryptophan; inhibition and stereoselectivity in the uptake of tyrosine by brain and muscle. J Biol Chem. 1962 Mar;237:803–806. [PubMed] [Google Scholar]
  11. Knott P. J., Curzon G. Free tryptophan in plasma and brain tryptophan metabolism. Nature. 1972 Oct 20;239(5373):452–453. doi: 10.1038/239452a0. [DOI] [PubMed] [Google Scholar]
  12. Lehmann J. Light--a source of error in the fluorometric determination of tryptophan. Scand J Clin Lab Invest. 1971 Sep;28(1):49–55. doi: 10.3109/00365517109090662. [DOI] [PubMed] [Google Scholar]
  13. Lipsett D., Madras B. K., Wurtman R. J., Munro H. N. Serum tryptophan level after carbohydrate ingestion: selective decline in non-albumin-bound tryptophan coincident with reduction in serum free fatty acids. Life Sci II. 1973 Jan 22;12(2):57–64. doi: 10.1016/0024-3205(73)90027-1. [DOI] [PubMed] [Google Scholar]
  14. Madras B. K., Cohen E. L., Fernstrom J. D., Larin F., Munro H. N., Wurtman R. J. Letter: Dietary carbohydrate increases brain tryptophan and decreases free plasma tryptophan. Nature. 1973 Jul 6;244(5410):34–35. doi: 10.1038/244034a0. [DOI] [PubMed] [Google Scholar]
  15. Madras B. K., Cohen E. L., Messing R., Munro H. N., Wurtman R. J. Relevance of free tryptophan in serum to tissue tryptophan concentrations. Metabolism. 1974 Dec;23(12):1107–1116. doi: 10.1016/0026-0495(74)90027-4. [DOI] [PubMed] [Google Scholar]
  16. Pérez-Cruet J., Chase T. N., Murphy D. L. Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan and neutral amino acids in humans. Nature. 1974 Apr 19;248(5450):693–695. doi: 10.1038/248693a0. [DOI] [PubMed] [Google Scholar]
  17. Rogers Q. R., Harper A. E. Amino acid diets and maximal growth in the rat. J Nutr. 1965 Nov;87(3):267–273. doi: 10.1093/jn/87.3.267. [DOI] [PubMed] [Google Scholar]
  18. Tagliamonte A., Biggio G., Vargiu L., Gessa G. L. Free tryptophan in serum controls brain tryptophan level and serotonin synthesis. Life Sci II. 1973 Mar 22;12(6):277–287. doi: 10.1016/0024-3205(73)90361-5. [DOI] [PubMed] [Google Scholar]
  19. WAALKES T. P., UDENFRIEND S. A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med. 1957 Nov;50(5):733–736. [PubMed] [Google Scholar]
  20. Zucker I. Light-dark rhythms in rat eating and drinking behavior. Physiol Behav. 1971 Feb;6(2):115–126. doi: 10.1016/0031-9384(71)90078-3. [DOI] [PubMed] [Google Scholar]

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