ABSTRACT
Crithidia, like trypanosomes and leishmania, has an iron-containing superoxide dismutase. The iron chelator N1,N6-bis (dihydroxybenzoyl)-1,6-diaminohexane proved to be a potent inhibitor of this enzyme. Inhibition of the crithidial superoxide dismutase by this compound was dependent on the presence of oxygen and associated with the formation of a complex which could not be dissociated by gel-filtration chromatography. We propose that this biscatecholic inhibitor is first oxidized to a quinone which then covalently modifies a nucleophilic residue on the enzyme. This compound was less effective as an inhibitor of a mammalian copper- and zinc-containing superoxide dismutase. Thus, this inhibitor could serve as a prototype for the design of antiparasitic agents.
Subject(s)
Chelating Agents/pharmacology , Crithidia/enzymology , Diamines/pharmacology , Hydroxybenzoates/pharmacology , Superoxide Dismutase/antagonists & inhibitors , Animals , Cattle , Chromatography, Gel , Copper , Erythrocytes/enzymology , Iron , Oxidation-Reduction , Oxygen , Spectrophotometry , ZincABSTRACT
Dialysed extracts of Tritrichomonas foetus were found to have superoxide dismutase at substantially higher levels than those found in trypanosomatids and mouse red blood cells. The activity was sensitive to inhibition by H2O2 but not by cyanide, suggesting that this organism has iron-containing superoxide dismutase(s). Three isozymes were seen by isoelectric focusing which appeared to be sensitive to inhibition by H2O2.
