title: The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease.
abstract: 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.
authors: Instituto de Investigaciones Biotecnologicas, Instituto Tecnologico de Chascomus, Provincia de Buenos Aires, Argentina.
authors: Mariana
authors: M
authors: Igoillo-Esteve
authors: Dante
authors: D
authors: Maugeri
authors: Ana L
authors: AL
authors: Stern
authors: Paula
authors: P
authors: Beluardi
authors: Juan J
authors: JJ
authors: Cazzulo
mesh_terms: D019880:Aldehyde-Ketone Transferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D007535:Isomerases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000235:genetics*; D016415:Sequence Alignment; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics
chemical_list: D010088:Oxidoreductases; D019880:Aldehyde-Ketone Transferases; D006867:Hydrolases; D007535:Isomerases