Capsaicin, a structural analog of tyrosine, inhibits the aminoacylation of tRNA(Tyr).
Because of its structural homology to capsaicin, the amino acid tyrosine appeared as a potential analog of the toxin and, consequently, could be a tool that could be used to clarify the mechanism of action of capsaicin. The in vitro experimental system was used to determine whether tyrosine and capsaicin effectively compete for tyrosyl-tRNA synthetase (extracted from mouse liver). The conditions for an efficient aminoacylation reaction were determined by kinetic tests and tests with different amounts of enzyme (in the absence of capsaicin). The reaction was fast and 40 microliters of the enzyme solution in a final reaction mixture volume of 100 microliters gave satisfactory results. The effect of different concentrations of capsaicin on the charging of [14C]tyrosine on its specific tRNA was tested for two concentrations of tyrosine (10 and 20 microM). The results obtained were represented in a Dixon plot and showed that capsaicin acts as a competitive and efficient inhibitor of tyrosyl-tRNA synthetase catalyzed reaction (Ki = 41.7 microM). The consequence of this inhibition in the whole animal and in cell culture remains to be determined and quantified. However, these results were supported by the fact that the capsaicin concentration that induced 50% of cell death was 48 microM for the toxin alone, whereas it was 96 microM when an equimolar concentration of tyrosine was added to capsaicin in the culture medium of hippocampal astrocytes.
Cochereau
C
C
Laboratory of Toxicology and Applied Hygiene, University of Bordeaux II, France.
Sanchez
D
D
Bourhaoui
A
A
Creppy
E E
EE
D000215:Acylation / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000494:pharmacology*; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors*
D014443:Tyrosine; D014448:Tyrosine-tRNA Ligase; D002211:Capsaicin