| Inhibition of aminoacyl-tRNA synthetases by p-chloroamphetamine and its role in protein synthesis inhibition. | |
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MedLine Citation:
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PMID: 6625607 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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p-Chloroamphetamine inhibited to some degree all amino acid-dependent pyrophosphate-exchange activities which could be detected in a rabbit reticulocyte extract. A detailed kinetic analysis of the reaction catalyzed by reticulocyte leucyl-tRNA synthetase demonstrated that the inhibitor affected only amino acid binding. Less rigorous studies of other synthetases from both rabbit reticulocyte and Escherichia coli could be similarly interpreted, suggesting that this compound interacts in a common manner with these several enzymes. The contribution of such effects to the inhibition of protein synthesis by the drug was investigated using cell-free translation systems in which rates of amino acid incorporation were limited to varying degrees by the synthesis and availability of aminoacyl-tRNA. In a wheat germ system programmed with globin mRNA, in which levels of amino acids and aminoacyl-tRNAs were shown to limit the rate of protein synthesis, the inhibition produced by p-chloroamphetamine could be partially reversed by increasing the concentration of the limiting amino acid. In a reticulocyte lysate, in which amino acid concentrations were not limiting, inhibition failed to show an amino acid-reversible component. Thus, while the inhibition of aminoacyl-tRNA synthetases by amphetamines can be shown in some cases to play a role in the effects of these compounds on in vitro protein synthesis, other sites of interference with initiation and/or elongation reactions may predominate, depending on the construction of the system under study. |
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Authors:
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T S Nowak; E B Albright; H N Munro |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 225 ISSN: 0003-9861 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 1983 Sep |
Date Detail:
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Created Date: 1983-11-23 Completed Date: 1983-11-23 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 722-30 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acyl-tRNA Synthetases
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antagonists & inhibitors* Amphetamines / pharmacology* Animals Kinetics Leucine-tRNA Ligase / antagonists & inhibitors* Magnesium / pharmacology Poly U / metabolism Protein Biosynthesis / drug effects* Rabbits Reticulocytes / drug effects, metabolism* Ribosomes / drug effects, metabolism* Seeds / drug effects, metabolism Triticum / metabolism p-Chloroamphetamine / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AM 07095-02/AM/NIADDK NIH HHS; AM 15364-05/AM/NIADDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amphetamines; 27416-86-0/Poly U; 64-12-0/p-Chloroamphetamine; 7439-95-4/Magnesium; EC 6.1.1.-/Amino Acyl-tRNA Synthetases; EC 6.1.1.4/Leucine-tRNA Ligase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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