55 research outputs found
Role of Δ1-Pyrroline-5-Carboxylate Dehydrogenase Supports Mitochondrial Metabolism and Host-Cell Invasion ofTrypanosoma cruzi
Proline is crucial for energizing critical events throughout the life cycle of Trypanosoma cruzi, the etiological agent of Chagas disease. The proline breakdown pathway consists of two oxidation steps, both of which producereducing equivalents as follows: the conversion of proline to Δ1-pyrroline-5-carboxylate (P5C), and the subsequent conversion of P5C to glutamate. We have identified and characterized the Δ1-pyrroline-5-carboxylate dehydrogenase from T. cruzi (TcP5CDH) and report here on how this enzyme contributes to a central metabolic pathway in this parasite. Size-exclusionchromatography, two-dimensional gel electrophoresis, and small angle x-ray scattering analysis of TcP5CDH revealed an oligomericstate composed of two subunits of six protomers. TcP5CDH was found to complement a yeast strain deficient in PUT2 activity,confirming the enzyme's functional role; and the biochemical parameters (Km, kcat, and kcat/Km) of the recombinant TcP5CDH were determined, exhibiting values comparable with those from T. cruzi lysates. In addition, TcP5CDH exhibited mitochondrial staining during the main stages of the T. cruzi life cycle. mRNA and enzymatic activity levels indicated the up-regulation (6-fold change) of TcP5CDH during the infectivestages of the parasite. The participation of P5C as an energy source was also demonstrated. Overall, we propose that thisenzymatic step is crucial for the viability of both replicative and infective forms of T. cruzi
Human liver glutamic Îł-semialdehyde dehydrogenase: Structural relationship to the yeast enzyme
Human brain “high Km” aldehyde dehydrogenase: Purification, characterization, and identification as NAD+-dependent succinic semialdehyde dehydrogenase
Structural basis of substrate selectivity of Δ1-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): Semialdehyde chain length
Succinic semialdehyde dehydrogenase from mammalian brain: Subunit analysis using polyclonal antiserum
Human Brain Glyceraldehyde-3-Phosphate Dehydrogenase, Succinic Semialdehyde Dehydrogenase and Aldehyde Dehydrogenase Isozymes: Substrate Specificity and Sensitivity to Disulfiram
- …