The relevance of the metabolism of glutamine in the cell biology and bioenergetics of Trypanosoma cruzi and Trypanosoma brucei

Abstract

The Trypanosoma cruzi is a causative agent of Chagas disease, also known as American tripanosomise. The Trypanosoma brucei is etiological agent of sleeping sickness also known as Africa tripanosomiase. T. cruzi is able to utilize carbohydrate and amino acids as carbon and energy source. The participation of amino acid in important biological process as proliferation, differentiation, cell invasion, and stress conditions resistance has been described. The importance of amino acids for Trypanosoma brucei has been described in procyclic forms, but little is known about bloodstream forms. Procyclic forms developed a metabolism based on consumption of amino acids as proline. Has been described that proline metabolism is essential for the parasite survival in the invertebrate host. The amino acid metabolism occurs with the production of NH4+. These parasites do not have the functional urea cycle, the ammonia may be excreted into the extracellular medium, or it can be transferred to ±-ketoglutarate forming glutamate, which acts as a donor of NH3 to pyruvate, forming alanine, a major product of amino acid metabolism. The synthesis of glutamine has glutamate and ammonia as substrates, this reaction is catalyzed by the enzyme glutamine synthetase, which can be involved in the ammonia detoxification in these parasites. The Glutamine may be a substrate for important pathways to parasite survival such as synthesis of pyrimidines, amino sugars, and GMP. The main goal of this project is to evaluate the relevance of the metabolism of glutamine in the cell biology and bioenergetics of Trypanosoma cruzi and Trypanosoma brucei using the CRISPR/cas9 to GS gene knockout in T. cruzi and RNAi to induce GS knockdown in T. brucei.