Characterization of the heme O, the heme A and enzymes homologous to COX10 and COX15 during intra-erythrocytic development of Plasmodium falciparum.

• Grant number: 12/20273-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2013
• Effective date (End): October 31, 2016
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Alejandro Miguel Katzin
• Grantee: Raquel Maria Simão Gurge
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Malaria is an important public health problem especially in tropical regions, because it is a leading cause of morbidity and mortality in humans. .The widespread and indiscriminate use of antimalarial has led to resistance of the parasite, which leads us to the need for developing new antimalarial drugs, this goal can be achieved by identifying new potential targets for malaria chemotherapy, requiring a thorough knowledge of biochemistry of Plasmodium. Our group has characterized several products of isoprenoid biosynthesis in P. falciparum.All isoprenoid molecules have as a basic unit of five carbons, (C5H9)n, known as isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP). The FPP is an intermediate and it is a substrate for the synthesis of several isoprenoids, such as ubiquinone and dolichol, and also can bind to a protein or a heme group.The heme is critical for survival of Apicomplexas, although its function in these organisms remain poorly understood. The Heme O and Heme A are the main compounds of aerobic respiration in mitochondria and bacteria also are used for oxygen reduction of heme-copper oxidases terminals.In the genome of P. falciparum were identified genes encoding homologous enzymes COX10 and COX15, proteins required for Heme O and heme A synthesis. Therefore, the characterization of these enzymes as well as the heme O and heme A would be fundamental to understand this biosynthetic pathway.

Academic Publications

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

GURGE, Raquel Maria Simão. Study of the farnesylated heme synthesis pathway in intra-erythrocyte stages of P. falciparum and inhibitors of this pathway.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.