Targeting glycolysis in the malaria parasite Plasmodium falciparum

Abstract:

Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand.

Citation: FEBS J 283(4) : 634

Date Published: 1st Feb 2016

Registered Mode: Not specified

Authors: David D. van Niekerk, Gerald P. Penkler, Francois du Toit, Jacky L. Snoep

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Citation
van Niekerk, D. D., Penkler, G. P., du Toit, F., & Snoep, J. L. (2016). Targeting glycolysis in the malaria parasitePlasmodium falciparum. In FEBS Journal (Vol. 283, Issue 4, pp. 634–646). Wiley. https://doi.org/10.1111/febs.13615
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Created: 30th Aug 2016 at 15:04

Last updated: 19th Sep 2016 at 15:26

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