{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T20:25:20Z","timestamp":1748636720262},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1989,1,5]],"date-time":"1989-01-05T00:00:00Z","timestamp":599961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[1990,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The transport of the eight amino acids (phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, histidine and methionine) using the large neutral amino acid transporter of the blood\u2010brain barrier (BBB) has been calculated using published kinetic data. The fate of the amino acids has been followed from blood to interstitial space, to cell and through metabolism which included, for tyrosine and tryptophan, the hydroxylases. The system was analysed in terms of flux control coefficients. Since the summation theorem did not hold, the system clearly behaved as a non\u2010homogeneous system. At physiological levels of these eight amino acids, the largest contribution to the control of the flux of tyrosine is given by the hydroxylase step, followed by the diffusional component of the transport across the BBB. For tryptophan it is the hydroxylase step, followed by the carrier\u2010mediated transport across the BBB. For the other amino acids it is the metabolism, followed by the diffusional component of the BBB transport.<\/jats:p><jats:p>These parameters for tyrosine and tryptophan were determined at increased levels of blood phenylalanine, tyrosine or histidine. The flux through tryptophan hydroxylase can be affected by high blood levels of tyrosine and histidine to values also observed in hyperphenylalaninaemia. Since hypertyrosinaemia (type II) and hyperhistidinaemia are not associated with mental retardation, it is concluded that interference with transport across the BBB of tyrosine and tryptophan, as well as the flux through tryptophan hydroxylase leading to the synthesis of 5\u2010hydroxytryptamine, do not contribute to the cause of permanent brain dysfunction in hyperphenylalaninaemia.<\/jats:p><jats:p>It can be calculated that addition of tyrosine to the diet to raise the blood tyrosine level in phenylketonuria patients may have a beneficial effect for the synthesis of neurotransmitters derived from tyrosine.<\/jats:p>","DOI":"10.1007\/bf01799331","type":"journal-article","created":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T13:55:43Z","timestamp":1119362143000},"page":"37-57","source":"Crossref","is-referenced-by-count":14,"title":["The control of 5\u2010hydroxytryptamine and dopamine synthesis in the brain: A theoretical approach"],"prefix":"10.1002","volume":"13","author":[{"given":"F. A.","family":"Hommes","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology Medical College of Georgia  Augusta GA 30912\u20102100 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology Medical College of Georgia  Augusta GA 30912\u20102100 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1989,1,5]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"203","volume-title":"Inherited Diseases of Amino Acid Metabolism. Recent Progress in the Understanding, Recognition and Management","author":"Buist N. R. 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