Energy production in Entamoeba histolytica: new perspectives in rational drug design.
The amebicidal action of metronidazole is activated when the enzyme pyruvate:ferredoxin oxido-reductase transfers reducing equivalents to the nitro group of the drug. The enzyme is present in Entamoeba 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 reductase in the human host. E. histolytica possesses other enzymes involved in glucose catabolism that are interesting for the rational design of new drugs. It has glycolytic enzymes that are important for the production of energy like phosphofructokinase, pyruvate phosphate dikinase, phosphoenolpyruvate carboxytransphosphorylase and acetate 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 the cloning 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 therapeutic research.
Saavedra-Lira
E
E
Departamento de Microbiología, Universidad Nacional Autónoma de México, México, D.F.
Pérez-Montfort
R
R
D000563:Amebicides / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism; D004748:Entamoeba histolytica / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004749:Entamoebiasis / Q000188:drug therapy / Q000469:parasitology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D016052:Protozoan Vaccines; D019289:Pyruvic Acid / Q000378:metabolism; D013045:Species Specificity
D000563:Amebicides; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019289:Pyruvic Acid