Diet-Induced Changes in Plasma Amino Acid Pattern: Effects on the Brain Uptake of Large Neutral Amino Acids, and on Brai
Tryptophan is transported into brain by a competitive carrier system it shares with such other large neutral amino acids as tyrosine, phenylalanine, leucine, isoleucine, and valine. Physiologic variations in the plasma neutral amino acid pattern (either a
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© by Springer-Verlag 1979
Diet-lnduced Changes in Plasma Amino Acid Pattern: Effects on the Brain U ptake of Large Neutral Amino Acids, and on Brain Serotonin Synthesis
J. D.
Fernstrom
Labaratory of Brain and Metabolism, Program in Neural and Endocrine Regulation, Massachusetts Institute of Technology, Cambridge, Massachusetts, U.S.A. With 6 Figures
Summary Tryptophan is transported into brain by a competitive carrier system it shares with such other large neutral amino acids as tyrosine, phenylalanine, leucine, isoleucine, and valine. Physiologie variations in the plasma neutral amino acid pattern (either as a change in plasma tryptophan, or in the plasma concentration of one or more of its competitors) directly alter this competitive process, and thereby modify the uptake of tryptophan into brain. Such variations in tryptophan uptake influence brain tryptophan Ievels, and thus serotonirr synthesis. Food intake, by influencing directly the plasma Ievels of large neutral amino acids, can therefore predictably modify brain tryptophan uptake and serotonirr synthesis. The effect of food intake on the competitive uptake of tryptophan into brain, and on brain tryptophan Ievels, has recently been shown not to be limited to this amino acid, but also holds for other large neutral amino acids, and for certain large neutral amino acid drugs (e.g., methyldopa). Hence, following a meal, the brain concentration of any large neutral amino acid appears to depend on how the food modifies the plasma Ievel of that amino acid relative to the plasma concentrations of its competitors. The binding of tryptophan to albumirr in blood has also been suggested to influence brain tryptophan uptake. However, this notion has not been sustained by the results of nutritional studies, in which meal-induced changes in brain tryptophan levels were readily shown not to be predicted by the alterations in the size of the serum free tryptophan pool. Taken together, these data affirm the importance of competitive transport in determining brain tryptophan uptake and Ievels, but question
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whether serum albumin binding and the size of the free tryptophan pool function physiologically to modulate brain tryptophan concentrations.
Diet has been known to influence brain serotonin (5-HT) levels for almost 20 years: long before kinetic data became available on tryptophan hydroxylase, numerous investigators had shown that cl1ronic increases or decreases in the availability of tryptophan to the body and brain produced elevations or reductions, respectively, in brain 5-HT (Zbinden et al., 1958; Gal and Drewes, 1962; Green et al., 1962). Moreover, even before good information was obtained on the Km of tryptophan hydroxylase for its substrate, a group of Scottish investigators demonstrated that the rapid increases in brain tryptophan levels that followed injection of the amino acid elicited sharp increases in the rate of 5-HT synthesis (Ashcrofi et al., 1965). When the kinetic data were finally obtained (]equier et al., 1969), what was alr
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