Bakker, Michels, Opperdoes, Westerhoff, 1997

Model Status

This model is overconstrained and is currently unable to be solved in available software. ValidateCellML also detects unit inconsistencies within the model.

Model Structure

Salivarian trypanosomes are extracellular parasites of the blood and tissue fluids of mammals. When it is within the bloodstream of its host Homo sapiens, Trypanosoma brucei, (the parasite that causes African sleeping disease in humans), displays very simple metabolism. In the bloodstream form (within its host) the parasite lacks a Krebs cycle and oxidative phosphorylation, and its metabolism is restricted to the glycolytic pathway alone. As in all trypansomes, most of the glycolytic enzymes of Trypanosoma brucei are contained within a specialised organelle called a glycosome (see the figure below). In addition to this structural difference beween trypanosomes and other eukaryotic cells, trypanosomes also display differences at the biochemical level of their metabolism. Their glycolitic pathway is simplier, with few side chains and reduced allosteric enzymatic regulation. These differences between the host and parasite metabolism make the glycolytic pathway a potential target for drugs against African sleeping disease.

Most of the glycolytic enzymes of Trypanosoma brucei have been isolated and kinetically characterised. From this experimental data, Bakker et al. developed a mathematical model of trypanosomal glycolysis. Model simulations predict how the steady-state glycolytic flux and metabolite concentrations depend on the substrate and product concentrations and the enzyme-kinetic parameters. The model explains certain aspects of cell physiology, but it does have its limitations. Further experimental data on the transmembrane flux dynamics of metabolites would help to improve the accuracey of the model.

The complete original paper reference is cited below:

Glycolysis in Bloodstream Form Trypanosoma brucei Can Be Understood in Terms of the Kinetics of the Glycolytic Enzymes, Barbara M. Bakker, Paul A. M. Michels, Fred R. Opperdoes, and Hans V. Westerhoff, 1997, The Journal of Biological Chemistry , 272, 3207-3215. (Full text and PDF versions of the article are available to subscribers of the JBC website.) PubMed ID: 9013556

The raw CellML description of the model of trypanosome glycolysis can be downloaded in various formats as described in .

The stoichiometric scheme of the model of glycolysis in the bloodstream form of the parasite Trypanosoma brucei.