GLUTATHIONE METABOLISM IN PROTOZOAN PARASITES. MAKING THE DIFFERENCE

ARIAS, DIEGO G.; MÁRQUEZ, VANINA E.; CABEZA, MATÍAS S.; IGLESIAS, ALBERTO A.; GUERRERO, SERGIO A.

Glutathione: Biochemistry, Mechanisms of Action and Clinical Implications

Nova Science Publisher

Año: 2012; p. 295 - 326

Generation of reactive oxygen species (ROS) is a common feature of abiotic and biotic stresses. ROS need to be detoxified to avoid the occurrence of deleterious reactions. Parasitic diseases such as sleeping sickness, Chagas disease, and malaria, between others, are major health problems in poverty-stricken areas. Redox metabolism in parasitic protozoa is a potentially relevant target for developing specific drug inhibitors. The design of efficacious and safe drugs is possible after the occurrence of metabolic pathways that are unique and essential to the parasite, but absent in the host. In most organisms, glutathione is the most abundant low-molecular weight thiol acting in cellular redox systems. In those parasites with deficit or lacking the glutathione machinery, other active molecules are functional in mimicking the former reductive compound. Many of the known glutathione-dependent processes are directly related to specific life-style of the respective parasite. Thus, malaria parasites have a dual antioxidant system based on glutathione and thioredoxin. Proteins involved in glutathione-dependent metabolic pathways include glutaredoxins, glyoxalases, thioredoxins, glutathione reductase and glutathione S‑transferases. In contrast, in trypanosomatids (Trypanosoma and Leishmania spp.), the redox network is centered around trypanothione.