Role of glutamine synthetase in the biology of Trypanosoma cruzi, and perspectives as a possible therapeutic target

• Grant number: 13/09851-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2014
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Ariel Mariano Silber
• Grantee: Flávia Silva Damasceno
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 15/09039-2 - Role of L-glutamine in the protection of Trypanosoma cruzi and Trypanosoma brucei against programmed cell death, BE.EP.DR

Abstract

Chagas disease, also known as American trypanosomiasis, is caused by the flagellate protozoan Trypanosoma cruzi and affects approximately 10 million people in endemic areas of Mexico, Central America and South T. cruzi is able to utilize carbohydrate and amino acids as carbon and energy source. 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, is catalyzed by enzyme glutamine synthetase, which can be involved in the detoxification of ammonia in the parasite. The importance of glutamine in the administration of nitrogen utilization, participation in energy metabolism and detoxification of ammonia in others cells was described. The glutamate-glutamine interconversion and importance in the biology of T. cruzi have not been studied. In general, this chemical conversion occurs in two steps: 1. Phosphorylation of glutamate producing ³-glutamyl phosphate 2. Amination of ³-glutamyl phosphate producing glutamine. These two steps are dependent on the presence of glutamine synthetase. Therefore, the aim this project is evaluate the importance of L-glutamine and glutamine synthetase in the biology of T. cruzi during the life cycle of the parasite and the perspectives as a new therapeutic target.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DAMASCENO, Flávia Silva. Role of glutamine in the biology of Trypanosoma cruzi and Trypanosoma brucei.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.