Tj. Schmidt, Glutathione adducts of helenalin and 11 alpha 3-dihydrohelenalin acetate inhibit glutathione S-transferase from horse liver, PLANTA MED, 66(2), 2000, pp. 106-109
The 2-mono- and 2,13-bis-glutathionyl adducts of helenalin and the 2-monogl
utathionyl adduct of 11 alpha,13-dihydrohelenalin acetate were previously s
hown to be formed by spontaneous Michael addition at physiological pH. In l
iving cells, glutathione (GSH) conjugation of many types of electrophilic a
gents is catalysed by a family of GSH S-transferase enzymes (CST). The capa
bility of a glutathione S-transferase from horse liver to catalyze the reac
tion of helenalin and other helenanolides with GSH was investigated. The en
zyme did not accelerate GSH conjugation of helenalin, 11 alpha,13-dihydrohe
lenalin, or 2-deacetyl-6-deoxychamissonolide. The GSH-adducts, formed by sp
ontaneous reaction, were found to be inhibitors of this enzyme. Free helena
lin, a potent inhibitor of many enzymes containing free sulfhydryl groups,
did not show any inhibitory activity on GST. It was thus demonstrated that
GSH-adducts of sesquiterpene lactones possess their own specific biological
activity. Two further enzymes using GSH as substrate, glutathione reductas
e and glyoxalase I, were not influenced by free helenalin or its GSH-adduct
s.