Construction and validation of a detailed kinetic model of glycolysis in Plasmodium falciparum
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BiBTeXThe enzymes in the Embden–Meyerhof–Parnas pathway of Plasmodium falciparum trophozoites were kinetically characterized and their integrated activities analyzed in a mathematical model. For validation of the model, we compared model predictions for steady-state fluxes and metabolite concentrations of the hexose phosphates with experimental values for intact parasites. The model, which is completely based on kinetic parameters that were measured for the individual enzymes, gives an accurate prediction of the steady-state fluxes and intermediate concentrations. This is the first detailed kinetic model for glucose metabolism in P. falciparum, one of the most prolific malaria-causing protozoa, and the high predictive power of the model makes it a strong tool for future drug target identification studies. The modelling workflow is transparent and reproducible, and completely documented in the SEEK platform, where all experimental data and model files are available for download.
SEEK ID: https://fairdomhub.org/publications/240
DOI: 10.1111/febs.13237
Projects: Whole body modelling of glucose metabolism in malaria patients
Publication type: Not specified
Journal: FEBS J
Citation: FEBS J 282(8) : 1481
Date Published: 1st Apr 2015
Registered Mode: Not specified
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Created: 9th Jul 2015 at 15:30
Last updated: 8th Dec 2022 at 17:26
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Projects: PSYSMO, MOSES, SysMO DB, SysMO-LAB, SulfoSys, SulfoSys - Biotec, Whole body modelling of glucose metabolism in malaria patients, FAIRDOM, Molecular Systems Biology, COMBINE Multicellular Modelling, HOTSOLUTE, Steroid biosynthesis, Yeast glycolytic oscillations, Computational pathway design for biotechnological applications, SCyCode The Autotrophy-Heterotrophy Switch in Cyanobacteria: Coherent Decision-Making at Multiple Regulatory Layers, Project Coordination, WP 3: Drug release kinetics study, Glucose metabolism in cancer cell lines
Institutions: Manchester Centre for Integrative Systems Biology, University of Manchester, University of Stellenbosch, University of Manchester - Department of Computer Science, Stellenbosch University
https://orcid.org/0000-0003-2633-0537
The Snoep Lab’s core research efforts are in Computational Systems Biology; a combined experimental, modeling and theoretical approach to quantitatively understand the functional behavior of Biological Systems resulting from the characteristics of their components. Our main focus is on metabolism, of human pathogens such as Plasmodium falciparum, Mycobacterium tuberculosis, but also of breast cancer cell lines, and on modelling disease states such as glucose homeostatis in type 2 diabetes, and ...
Projects: Whole body modelling of glucose metabolism in malaria patients, Steroid biosynthesis, Yeast glycolytic oscillations, Computational pathway design for biotechnological applications, Glucose metabolism in cancer cell lines
Web page: http://www.sun.ac.za/english/faculty/science/biochemistry/research/snoep-group
Hypoglycaemia and lactic acidosis are key diagnostics for poor chances of survival in malaria patients. In this project we aim to test to what extent the metabolic activity of Plasmodium falciparum contributes to a changed glucose metabolism in malaria patients. The approach is to start with detailed bottom up models for the parasite and then merge these with more coarse grained models at the whole body level.
Programme: SARCHI: Mechanistic modelling of health and epidemiology
Public web page: Not specified
The investigation entails the construction and validation of a detailed mathematical model for glycolysis of the malaria parasite Plasmodium falciparum in the blood stage trophozoite form.
Submitter: Dawie van Niekerk
Studies: Model analysis, Model construction, Model validation
Assays: ALD, ATPASE, Culturing and synchronisation of P. falciparum, ENO, G3PDH, GAPDH, GLC incubation, GLCtr, GLYtr, HK, Inhibition of glucose transport, Inhibition of lactate flux, LACtr, LDH, PFK, PGI, PGK, PGM, PK, PYRtr, Steady state, Supply-demand analysis, TPI, Trophozoite Isolation and Lysate Preparation
Submitter: Dawie van Niekerk
Investigation: Glucose metabolism in Plasmodium falciparum tro...
Assays: Inhibition of glucose transport, Inhibition of lactate flux, Supply-demand analysis
This study includes the experimental data for model validation and the model predictions of that data set.
Submitter: Dawie van Niekerk
Investigation: Glucose metabolism in Plasmodium falciparum tro...
Assays: GLC incubation, Steady state
This study includes all the experimental data, SOPs and modelling files for the individual reactions used for the model construction.
