ArticleThe Journal of biological chemistry2015
Role of Δ1-pyrroline-5-carboxylate dehydrogenase supports mitochondrial metabolism and host-cell invasion of Trypanosoma cruzi.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Evolutionary and Structural Insights into Proline Metabolism Genes Associated with Salt Resilience in Mango.Biochemical genetics · 2026Article
- "L-Ornithine Liposomal Nanoparticles Targeting the Proline Cycle: A Mechanistic Perspective for Ammonia-Driven Hepatic Encephalopathy".Cell biochemistry and biophysics · 2026Review
- In Vivo Trypanocidal Activity of the Drug Disulfiram Combined with Benznidazole.ACS infectious diseases · 2026Article
- Quantification of Mitochondrial Pyrroline-5-Carboxylate in Arabidopsis Under Pseudomonas Syringae Infection.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Proline dehydrogenase, a rate-limiting catabolic enzyme, affecting the growth and pathogenicity of Toxoplasma gondii tachyzoites by regulating the proline metabolism and mitochondrial function of the parasite.Parasites & vectors · 2025Article
- Energy metabolism inmBio · 2025Review
- The role of l-serine and l-threonine in the energy metabolism and nutritional stress response ofmSphere · 2025Article
- Knocking out histidine ammonia-lyase by using CRISPR-Cas9 abolishes histidine role in the bioenergetics and the life cycle ofMicrobial cell (Graz, Austria) · 2025Article
- Branched-chain amino acids modulate the proteomic profile of Trypanosoma cruzi metacyclogenesis induced by proline.PLoS neglected tropical diseases · 2024Article
- In silico prediction of the metabolism of Blastocrithidia nonstop, a trypanosomatid with non-canonical genetic code.BMC genomics · 2024Article
- Article
- Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi.PLoS pathogens · 2021Article
- The Multifaceted Roles of Proline in Cell Behavior.Frontiers in cell and developmental biology · 2021Review
- Genome-scale metabolic models highlight stage-specific differences in essential metabolic pathways in Trypanosoma cruzi.PLoS neglected tropical diseases · 2020Article
- Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis inMolecules (Basel, Switzerland) · 2020Article
- Measurement of Energy States of the Trypanosomatid Mitochondrion.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development.Frontiers in chemistry · 2020Article
- Diminished Prolinemia in Chronic Chagasic Patients: A New Clue for Disease Pathology?Molecules (Basel, Switzerland) · 2019Article
- Role of Proline in Pathogen and Host Interactions.Antioxidants & redox signaling · 2019Review
- Characterization and functionality of two members of the SPFH protein superfamily, prohibitin 1 and 2 in Leishmania major.Parasites & vectors · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 produce reducing equivalents as follows: the conversion of proline to Δ(1)-pyrroline-5-carboxylate (P5C), and the subsequent conversion of P5C to glutamate. We have identified and characterized the Δ(1)-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-exclusion chromatography, two-dimensional gel electrophoresis, and small angle x-ray scattering analysis of TcP5CDH revealed an oligomeric state 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 infective stages of the parasite. The participation of P5C as an energy source was also demonstrated. Overall, we propose that this enzymatic step is crucial for the viability of both replicative and infective forms of T. cruzi.
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