A detailed kinetic model of glycolysis in Plasmodium falciparum-infected red blood cells for antimalarial drug target identification.
| Autor: | van Niekerk DD; Department of Biochemistry, Stellenbosch University, Matieland, South Africa., du Toit F; Department of Biochemistry, Stellenbosch University, Matieland, South Africa., Green K; Department of Biochemistry, Stellenbosch University, Matieland, South Africa., Palm D; Department of Biochemistry, Stellenbosch University, Matieland, South Africa., Snoep JL; Department of Biochemistry, Stellenbosch University, Matieland, South Africa; Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands. Electronic address: jls@sun.ac.za. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2023 Sep; Vol. 299 (9), pp. 105111. Date of Electronic Publication: 2023 Jul 29. |
| DOI: | 10.1016/j.jbc.2023.105111 |
| Abstrakt: | Upon infection by the malaria parasite Plasmodium falciparum, the glycolytic rate of a red blood cell increases up to 100-fold, possibly contributing to lactic acidosis and hypoglycemia in patients with severe malaria. This dramatic increase in glucose uptake and metabolism was correctly predicted by a newly constructed detailed enzyme kinetic model of glucose metabolism in the trophozoite-infected red blood cell. Subsequently, we expanded the model to simulate an infected red blood cell culture, including the different asexual blood-stage forms of the malaria parasite. The model simulations were in good agreement with experimental data, for which the measured parasitic volume was an important parameter. Upon further analysis of the model, we identified glucose transport as a drug target that would specifically affect infected red blood cells, which was confirmed experimentally with inhibitor titrations. This model can be a first step in constructing a whole-body model for glucose metabolism in malaria patients to evaluate the contribution of the parasite's metabolism to the disease state. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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