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Hysteresis of pyruvate phosphate dikinase from Trypanosoma cruzi

  • Protozoology - Original Paper
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Abstract

Trypanosoma cruzi, the causative agent of Chagas’ disease, belongs to the Trypanosomatidae family. The parasite undergoes multiple morphological and metabolic changes during its life cycle, in which it can use both glucose and amino acids as carbon and energy sources. The glycolytic pathway is peculiar in that its first six or seven steps are compartmentalized in glycosomes, and has a two-branched auxiliary glycosomal system functioning beyond the intermediate phosphoenolpyruvate (PEP) that is also used in the cytosol as substrate by pyruvate kinase. The pyruvate phosphate dikinase (PPDK) is the first enzyme of one branch, converting PEP, PPi, and AMP into pyruvate, Pi, and ATP. Here we present a kinetic study of PPDK from T. cruzi that reveals its hysteretic behavior. The length of the lag phase, and therefore the time for reaching higher specific activity values is affected by the concentration of the enzyme, the presence of hydrogen ions and the concentrations of the enzyme’s substrates. Additionally, the formation of a more active PPDK with more complex structure is promoted by it substrates and the cation ammonium, indicating that this enzyme equilibrates between the monomeric (less active) and a more complex (more active) form depending on the medium. These results confirm the hysteretic behavior of PPDK and are suggestive for its functioning as a regulatory mechanism of this auxiliary pathway. Such a regulation could serve to distribute the glycolytic flux over the two auxiliary branches as a response to the different environments that the parasite encounters during its life cycle.

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Acknowledgments

We thank Dr. Frédéric Bringaud for providing the monoclonal anti-T. brucei PPDK antibody and Dr. Paul Michels for his helpful comments on the manuscript.

Funding

This work was partially financially supported by the Science Technology and Innovation National Found (FONACIT – Fondo Nacional de Ciencia y Tecnología), within a Biotechnology scholarship (contract N°200600466); and by the Instituto Venezolano de Investigaciones Científicas (IVIC), project N°305.

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Authors and Affiliations

  1. Laboratorio de Enzimología de Parásitos, Facultad de Ciencias, Universidad de Los Andes, La Hechicera, Mérida, Venezuela

    Eglys González-Marcano, Hector Acosta, Wilfredo Quiñones & Juan Luis Concepción

  2. Laboratorio de Fisiología de Parásitos, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela

    Alfredo Mijares

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  1. Eglys González-Marcano
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  2. Hector Acosta
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  3. Wilfredo Quiñones
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  4. Alfredo Mijares
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  5. Juan Luis Concepción
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Eglys González-Marcano, Hector Acosta and Wilfredo Quiñones. The first draft of the manuscript was written by Eglys González-Marcano and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Eglys González-Marcano.

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Section Editor: Dana Mordue

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González-Marcano, E., Acosta, H., Quiñones, W. et al. Hysteresis of pyruvate phosphate dikinase from Trypanosoma cruzi. Parasitol Res 120, 1421–1428 (2021). https://doi.org/10.1007/s00436-020-06934-7

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  • DOI: https://doi.org/10.1007/s00436-020-06934-7

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