Caracterización bioquímica de la aldo-ceto reductasa de Trypanosoma cruzi (TcAKR) con actividad de quinona óxido reductasa. Determinación de su participación en el mecanismo de acción tripanocida de las o-naftoquinonas: postulación del rol fisiológico de esta enzima
Evidence indicates that the mechanism of action of drugs currently used for Chagas disease treatment, nifurtimox and benznidazole, and also naphthoquinones (NQs) involves their reduction by parasite reductases. In this regard, we have previously identified the NADPH-dependent aldo-keto reductase fro...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | |
| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
| Publicado: |
Facultad de Farmacia y Bioquímica
2018
|
| Materias: | |
| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_5795 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_5795.dir/5795.PDF |
| Aporte de: |
| Sumario: | Evidence indicates that the mechanism of action of drugs currently used for Chagas disease treatment, nifurtimox and benznidazole, and also naphthoquinones (NQs) involves their reduction by parasite reductases. In this regard, we have previously identified the NADPH-dependent aldo-keto reductase from Trypanosoma cruzi, the ethiological agent of this disease, denominated TcAKR. In order to investigate whether TcAKR participates in metabolism of trypanocidal drugs, the aims of this thesis were: i- perform biological and biochemical characterization of TcAKR, i- evaluate its participation in the action mechanism of trypanocidal drugs and ii-elucidate its physiological role. Results indicate that TcAKR is an oligomeric, cytosolic protein that is expressed in all stages of the parasite. TcAKR has reductase activity with o-NQs, among them, the trypanocidal agent ?-lapachona, with free radical production and also with benznidazole. Studies with TcAKR-overexpressing epimastigotes suggest that this enzyme is involved in ?-lapachona activation and, conversely, in benznidazole detoxification. Regarding TcAKR physiological function, hints are given that this enzyme may participate in glycerol catabolism fulfilling the role of glycerol dehydrogenase. |
|---|