ENERGY-PRODUCTION IN ENTAMOEBA-HISTOLYTICA - NEW PERSPECTIVES IN RATIONAL DRUG DESIGN

The amebicidal action of metronidazol is activated when the enzyme pyr uvate:ferredoxin oxido-reductase transfers reducing equivalents to the nitro group of the drug. The enzyme is present in Entamoeba histolyti ca and other anaerobic parasites like Giardia and Trichomonas that lac k mitochondria. The selectivity of the drug can be ascribed to the abs ence of the reductase in the human host. E. histolytica possesses othe r enzymes involved in glucose catabolism that are interesting for the rational design of new drugs. It has glycolytic enzymes that are impor tant for the production of energy like phosphofructokinase, pyruvate p hosphate dikinase, phosphoenolpyruvate carboxytransphosphorylase and a cetate thiokinase, which use pyrophosphate as a phosphate donor and ha ve no human counterparts. The first part of this article describes the reactions by which E. histolytica obtains energy from glucose degrada tion, and includes recent advances in the cloning of genes for the var ious participating enzymes. The second part shows an alternative view for the study of target enzymes that are unique to the parasite, and i ndicates their importance in therapeutic research.