The control of 5-hydroxytryptamine and dopamine synthesis in the brain: a theoretical approach

Journal of Inherited Metabolic Disease
F A Hommes, J S Lee

Abstract

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-brain 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-homogeneous 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-mediated transport across the BBB. For the other amino acids it is the metabolism, followed by the diffusional component of the BBB transport. 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 an...Continue Reading

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Citations

Feb 1, 1992·Amino Acids·M Hjelm, J Seakins
Oct 1, 1995·Pharmacology, Biochemistry, and Behavior·V CastagneM Gyger
Dec 1, 1996·Pharmacology, Biochemistry, and Behavior·V CastagneM Gyger
Dec 1, 1991·Biochemical Medicine and Metabolic Biology·F A Hommes
Jun 28, 2000·Molecular Genetics and Metabolism·W B HanleyJ T Clarke
Nov 11, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H E MöllerK Ullrich

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