Characterization and biological role of the catabolism of Cystein in Trypanosoma cruzi.

• Grant number: 24/06474-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Jessica Jenireth Rodriguez Duran
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/12938-0 - Amino acid metabolism in Trypanosoma cruzi: a toolbox to survive in hostile environments, AP.TEM

Abstract

The conversion of Cysteine (Cys) to Pyruvate (Pyr) can be carried out by two enzymes: a broad-spectrum substrate Aspartate aminotransferase (ASAT), which includes Cys among its substrates, and a Mercaptopyruvate Sulfotransferase (MPST). Due to their characteristics, the ASAT enzymes in T. cruzi are potential candidates for catalyzing the deamination reaction of Cys. However, despite the existence of putative sequences for these enzymes in the T. cruzi genome, there is currently no literature data showing the active pathway. The goal of this project is to confirm the existence of this "direct" pathway for Pyruvate production from Cys, as well as the possible dual connection between Serine (Ser) and Cysteine: through the enzyme cystathionine-²-synthase (CBS), Serine could be converted to Cysteine (and subsequently to Pyruvate). Conversely, through the enzyme Cysteine-³-lyase (CGL) and the reverse action of CBS, Cysteine could provide Serine, which could also contribute to Pyruvate production via Serine dehydrogenase. The reason for the co-existence of both pathways is not clear, as it appears that both serve the primary function of supplying Pyruvate-one using Ser and the other using Cys as intermediates.