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Clinical Relevance of Drugs Affecting Tryptophan Transport

Clinical Relevance of Drugs Affecting Tryptophan Transport R. Paoletti, C Sirtori Jr., and P. F. Spano Institute of Pharmacology and Pharmacognosy, University of Milan, Milan 20129, Italy FREE AND BOUND TRYPTOPHAN IN PLASMA Tryptophan is the only circulating amino acid highly bound to serum proteins (1). The plasma free fraction of serum tryptophan is very important for the control of the tryptophan pool in the brain (2, 2a, 3). In fact the rate of synthesis of serotonin (5-hydroxytryptamine, 5HT) in the brain is regulated principally by the availability of free L-tryptophan, whose normal concentration in the CNS is considerably below the Km of tryptophan hydroxylase, the first enzyme in 5HT biosynthesis (3-5), which has been considered the rate-limiting step (6). An increase of SHT turnover-as indicated by elevated concentrations of its metabolite S-hydroxyindoleacetic acid (SHIAA) -is frequently correlated to an increase in brain tryptophan, as observed in rats receiving drugs stimulating brain 5HT synthesis (3), submitted to prolonged fasting (7, 8) or immobilized (9). No consistent correlations have been found, however, between brain and plasma total tryptophan concentrations. For example, food deprivation or immobilization induce a significant increase in rat brain tryptophan, in spite of the well-known fact that mammalian tissues are unable to synthesize http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Pharmacology and Toxicology Annual Reviews

Clinical Relevance of Drugs Affecting Tryptophan Transport

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Publisher
Annual Reviews
Copyright
Copyright 1975 Annual Reviews. All rights reserved
Subject
Review Articles
ISSN
0362-1642
eISSN
1545-4304
DOI
10.1146/annurev.pa.15.040175.000445
pmid
1096797
Publisher site
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Abstract

R. Paoletti, C Sirtori Jr., and P. F. Spano Institute of Pharmacology and Pharmacognosy, University of Milan, Milan 20129, Italy FREE AND BOUND TRYPTOPHAN IN PLASMA Tryptophan is the only circulating amino acid highly bound to serum proteins (1). The plasma free fraction of serum tryptophan is very important for the control of the tryptophan pool in the brain (2, 2a, 3). In fact the rate of synthesis of serotonin (5-hydroxytryptamine, 5HT) in the brain is regulated principally by the availability of free L-tryptophan, whose normal concentration in the CNS is considerably below the Km of tryptophan hydroxylase, the first enzyme in 5HT biosynthesis (3-5), which has been considered the rate-limiting step (6). An increase of SHT turnover-as indicated by elevated concentrations of its metabolite S-hydroxyindoleacetic acid (SHIAA) -is frequently correlated to an increase in brain tryptophan, as observed in rats receiving drugs stimulating brain 5HT synthesis (3), submitted to prolonged fasting (7, 8) or immobilized (9). No consistent correlations have been found, however, between brain and plasma total tryptophan concentrations. For example, food deprivation or immobilization induce a significant increase in rat brain tryptophan, in spite of the well-known fact that mammalian tissues are unable to synthesize

Journal

Annual Review of Pharmacology and Toxicology – Annual Reviews

Published: Apr 1, 1975

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