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Molecular Pharmacology, Vol 3, 274-278, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Tryptophan Hydroxylase Inhibition: the Mechanism by Which p-Chlorophenylalanine Depletes Rat Brain Serotonin

ERIC JÉQUIER 1, WALTER LOVENBERG 1, and ALBERT SJOERDSMA 1

1 Experimental Therapeutics Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland 20014

Administration of the specific serotonin depletor p-chlorophenylalanine to rats results in marked inhibition of tryptophan hydroxylase of the brain. The enzyme inhibition can be correlated with and is assumed to be responsible for brain serotonin depletion. Although p-chlorophenylalanine is a competitive inhibitor of tryptophan hydroxylase in vitro, it causes an irreversible inactivation of the enzyme in vivo. The findings also support the conclusion that tryptophan hydroxylation is the rate-limiting enzymic step in serotonin biosynthesis.

Note:
ACKNOWLEDGMENT The authors would like to thank Dr. Sidney Udenfriend for helpful discussions during the course of this work.

Submitted on January 18, 1967




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