The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease
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Academia Brasileira de Ciências
2007
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| author | Mariana Igoillo-Esteve |
| author_facet | Mariana Igoillo-Esteve |
| contents | The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease Mariana Igoillo-Esteve Dante Maugeri Ana L. Stern Paula Beluardi Juan J. Cazzulo Multidisciplinaria (Ciencias Naturales y Exactas) Chagas disease oxidative stress NADPH generation Trypanosoma cruzi pentose phosphate pathway Trypanosoma cruzi is highly sensitive to oxidative stress caused by reactive oxygen species. Trypanothione, theparasites major protection against oxidative stress, is kept reduced by trypanothione reductase, using NADPH; themajor source of the reduced coenzyme seems to be the pentose phosphate pathway. Its seven enzymes are presentin the four major stages in the parasites biological cycle; we have cloned and expressed them in Escherichia colias active proteins. Glucose 6-phosphate dehydrogenase, which controls glucose flux through the pathway by itsresponse to the NADP/NADPH ratio, is encoded by a number of genes per haploid genome, and is induced up to46-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 copyper haploid genome. 6-phosphogluconate dehydrogenase is very unstable, but was stabilized introducing two saltbridges by site-directed mutagenesis. Ribose-5-phosphate isomerase belongs to Type B; genes encoding Type Aenzymes, present in mammals, are absent. Ribulose-5-phosphate epimerase is encoded by two genes. The enzymesof the pathway have a major cytosolic component, although several of them have a secondary glycosomal localization,and also minor localizations in other organelles. 2007 artículo científico 0001-3765 https://www.redalyc.org/articulo.oa?id=32779407 en http://www.redalyc.org/revista.oa?id=327 Anais da Academia Brasileira de Ciências application/pdf Academia Brasileira de Ciências Anais da Academia Brasileira de Ciências (Brasil) Num.4 Vol.79 |
| format | Artículo científico |
| id | redalyc_32779407 |
| institution | Redalyc |
| language | en |
| publishDate | 2007 |
| publisher | Academia Brasileira de Ciências |
| spellingShingle | The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease Mariana Igoillo-Esteve Multidisciplinaria (Ciencias Naturales y Exactas) Chagas disease oxidative stress NADPH generation Trypanosoma cruzi pentose phosphate pathway The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease Mariana Igoillo-Esteve Dante Maugeri Ana L. Stern Paula Beluardi Juan J. Cazzulo Multidisciplinaria (Ciencias Naturales y Exactas) Chagas disease oxidative stress NADPH generation Trypanosoma cruzi pentose phosphate pathway Trypanosoma cruzi is highly sensitive to oxidative stress caused by reactive oxygen species. Trypanothione, theparasites major protection against oxidative stress, is kept reduced by trypanothione reductase, using NADPH; themajor source of the reduced coenzyme seems to be the pentose phosphate pathway. Its seven enzymes are presentin the four major stages in the parasites biological cycle; we have cloned and expressed them in Escherichia colias active proteins. Glucose 6-phosphate dehydrogenase, which controls glucose flux through the pathway by itsresponse to the NADP/NADPH ratio, is encoded by a number of genes per haploid genome, and is induced up to46-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 copyper haploid genome. 6-phosphogluconate dehydrogenase is very unstable, but was stabilized introducing two saltbridges by site-directed mutagenesis. Ribose-5-phosphate isomerase belongs to Type B; genes encoding Type Aenzymes, present in mammals, are absent. Ribulose-5-phosphate epimerase is encoded by two genes. The enzymesof the pathway have a major cytosolic component, although several of them have a secondary glycosomal localization,and also minor localizations in other organelles. 2007 artículo científico 0001-3765 https://www.redalyc.org/articulo.oa?id=32779407 en http://www.redalyc.org/revista.oa?id=327 Anais da Academia Brasileira de Ciências application/pdf Academia Brasileira de Ciências Anais da Academia Brasileira de Ciências (Brasil) Num.4 Vol.79 |
| title | The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease |
| topic | Multidisciplinaria (Ciencias Naturales y Exactas) Chagas disease oxidative stress NADPH generation Trypanosoma cruzi pentose phosphate pathway |
| url | https://www.redalyc.org/articulo.oa?id=32779407 |