| The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease. | |
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MedLine Citation:
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PMID: 18066434 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Trypanosoma cruzi is highly sensitive to oxidative stress caused by reactive oxygen species. Trypanothione, the parasite's major protection against oxidative stress, is kept reduced by trypanothione reductase, using NADPH; the major source of the reduced coenzyme seems to be the pentose phosphate pathway. Its seven enzymes are present in the four major stages in the parasite's biological cycle; we have cloned and expressed them in Escherichia coli as active proteins. Glucose 6-phosphate dehydrogenase, which controls glucose flux through the pathway by its response to the NADP/NADPH ratio, is encoded by a number of genes per haploid genome, and is induced up to 46-fold by hydrogen peroxide in metacyclic trypomastigotes. The genes encoding 6-phosphogluconolactonase, 6-phosphogluconate dehydrogenase, transaldolase and transketolase are present in the CL Brener clone as a single copy per haploid genome. 6-phosphogluconate dehydrogenase is very unstable, but was stabilized introducing two salt bridges by site-directed mutagenesis. Ribose-5-phosphate isomerase belongs to Type B; genes encoding Type A enzymes, present in mammals, are absent. Ribulose-5-phosphate epimerase is encoded by two genes. The enzymes of the pathway have a major cytosolic component, although several of them have a secondary glycosomal localization, and also minor localizations in other organelles. |
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Authors:
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Mariana Igoillo-Esteve; Dante Maugeri; Ana L Stern; Paula Beluardi; Juan J Cazzulo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anais da Academia Brasileira de Ciências Volume: 79 ISSN: 0001-3765 ISO Abbreviation: An. Acad. Bras. Cienc. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-12-10 Completed Date: 2008-04-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503280 Medline TA: An Acad Bras Cienc Country: Brazil |
Other Details:
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Languages: eng Pagination: 649-63 Citation Subset: IM |
Affiliation:
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Instituto de Investigaciones Biotecnologicas, Instituto Tecnologico de Chascomus, Provincia de Buenos Aires, Argentina. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldehyde-Ketone Transferases
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genetics,
metabolism Amino Acid Sequence Animals Chagas Disease / drug therapy Hydrolases / genetics, metabolism Isomerases / genetics, metabolism Molecular Sequence Data Oxidation-Reduction Oxidoreductases / genetics, metabolism Pentose Phosphate Pathway / genetics* Sequence Alignment Trypanosoma cruzi / enzymology*, genetics |
| Chemical | |
Reg. No./Substance:
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EC 1.-/Oxidoreductases; EC 2.2.-/Aldehyde-Ketone Transferases; EC 3.-/Hydrolases; EC 5.-/Isomerases |
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