ABSTRACT
The amebicidal action of metronidazol is activated when the enzyme pyruvate: ferredoxin oxido reductase transfers reducing equivalents to the nitro group of the drug. The enzyme is present in Entanoeba histolytica and other anaerobic parasites like Giardia and Trichomonas that lack mitochondria. The selectivity of the drug can be ascribed to the absence of the reductasa in the human host. E. histolytica possesses other enzymes involved in glucose catabolism that are interesting for the rational desing of new drugs. It has glycolytic enzymes that are important for the production of energy like phosphofructokinase, pyruvate phosphate dikinase, phosphoenolpyruvate carboxytransphosphorylase and thiokinase, which use pyrophosphate as a phosphate donor and have no human counterparts. The first part of this article describes the reactions by which E. histolytica obtains energy from glucose degradation, and includes recent advances in thecloning of genes for the various participating enzymes. The second part shows an alternative view for the study of target enzymes that are unique to the parasite, and indicates their importance in therapautic research
Subject(s)
Amebiasis/enzymology , Amebicides/pharmacology , Carbohydrates/metabolism , Drug Design , Entamoeba histolytica/cytology , Enzymes/analysis , Nitroimidazoles , Parasitic Diseases/therapy , Pyruvates/metabolism , Electron Transport/physiologyABSTRACT
Amebiasis is one of the main causes worldwide of morbidity and mortality by parasites. Application of recombinant DNA technology to the study of Entamoeba histolytica is bringing new light into our understanding of this remarkable protozoan parasite and of the disease it causes. New achievements affect the way we approach many essential questions about E. histolytica, form the mechanism of its pathogenicity to the definition of E. hitolytica as a separate species from the nonpathogenic E. dispar. To give a single example, transfection of trophozoites is now possible and a new generation of studies taking advantage of this capability of manipulation is expected in the short term. Our goal with this review is to provide an updated and simple guide to the growing information on the molecular biology of E. histolytica