Biological role of the intermediary enzymes of the catabolism of Branched Chain Amino Acids in Trypanosoma cruzi.

• Grant number: 19/01227-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2019
• End date: August 31, 2020
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Carlos Adriano de Matos e Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/06034-2 - The biological role of amino acids and their metabolites in Trypanosoma cruzi, AP.TEM

Abstract

As cvan be seen in the body of the Project, the catabolism of the Branched Chain Amino Acids (BCAA) is complex and involves a big number of enzymes. The first steps of this pathway are being studied by two graduate students. Thus, we propose here to continue analyzing the pathway by studying the enzymes Metilcrotonoil-CoA Carboxilase, Metilglutaconil-CoA Hidratase, 3-Hidroxiisobutiril-CoA Hidrolase (which are specific for the conversion of Leu into Acetyl-CoA and Acetoacetate). The metabolism of Ile and Val still has an additional step catalysed by a shared enzyme: an Enoyl-CoA Hidratase. From this point, both amino acids can render Acetyl-CoA or Propanoyl-CoA through the enzymes 3-Hidroxiisobutiril-CoA Hidrolase, 3-Hidroxyacyl-CoA Dehydrogenase, Acetil-CoA C-Acyltransferase e Metylmalonate-semialdehyde Dehydrogenase (CoA-acylating). In summary, all the final products of the catabolism of the BCAA can be used as energy sources and can be used for the biosynthesis of fatty acids. This project aims to characterize the enzymes involved as well as their role in the parasite metabolism and resistance to metabolic stress.