CAPSAICIN, A STRUCTURAL ANALOG OF TYROSINE, INHIBITS THE AMINOACYLATION OF TRNA(TYR)

Because of its structural homology to capsaicin, the amino acid tyrosi ne appeared as a potential analog of the toxin and, consequently, coul d be a tool that could be used to clarify the mechanism of action of c apsaicin, The in vitro experimental system was used to determine wheth er tyrosine and capsaicin effectively compete for tyrosyl-tRNA synthet ase (extracted from mouse liver), The conditions for an efficient amin oacylation reaction were determined by kinetic tests and tests with di fferent amounts of enzyme (in the absence of capsaicin). The reaction was fast and 40 mu l of the enzyme solution in a final reaction mixtur e volume of 100 mu l gave satisfactory results, The effect of differen t concentrations of capsaicin on the charging of [C-14]tyrosine on its specific tRNA was tested for two concentrations of tyrosine (10 and 2 0 mu M). The results obtained were represented in a Dixon plot and sho wed that capsaicin acts as a competitive and efficient inhibitor of ty rosyl-tRNA synthetase catalyzed reaction (K-i = 41.7 mu M). The conseq uence of this inhibition in the whole animal and in cell culture remai ns to be determined and quantified. However, these results were suppor ted by the fact that the capsaicin concentration that induced 50% of c ell death was 48 mu M for the toxin alone, whereas it was 96 mu M when an equimolar concentration of tyrosine was added to capsaicin in the culture medium of hippocampal astrocytes. (C) 1996 Academic Press, Inc .