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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 104, No. 8, 2009, pp. 1100-1110
Bioline Code: oc09224
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 104, No. 8, 2009, pp. 1100-1110

 en A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi check for this species in other resources genome information
Alves-Ferreira, Marcelo; Guimarães, Ana Carolina Ramos; Capriles, Priscila Vanessa da Silva Zabala; Dardenne, Laurent E & Degrave, Wim M

Abstract

The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi check for this species in other resources to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite’s metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silico comparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.

Keywords
Trypanosoma cruzi - metabolism - metabolic pathways - drug target - analogous enzyme

 
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