GLYCOLYSIS IN BLOOD-STREAM FORM TRYPANOSOMA-BRUCEI CAN BE UNDERSTOOD IN TERMS OF THE KINETICS OF THE GLYCOLYTIC-ENZYMES

In trypanosomes the first part of glycolysis takes place in specialize d microbodies, the glycosomes. Most glycolytic enzymes of Trypanosoma brucei have been purified and characterized kinetically. In this paper a mathematical model of glycolysis in the bloodstream form of this or ganism is developed on the basis of all available kinetic data. The fl uxes and the cytosolic metabolite concentrations as predicted by the m odel were in accordance with available data as measured in non-growing trypanosomes, both under aerobic and under anaerobic conditions. The model also reproduced the inhibition of anaerobic glycolysis by glycer ol, although the amount of glycerol needed to inhibit glycolysis compl etely was lower than experimentally determined. At low extracellular g lucose concentrations the intracellular glucose concentration remained very low, and only at 5 mM of extracellular glucose, free glucose sta rted to accumulate intracellularly, in close agreement with experiment al observations. This biphasic relation could be related to the large difference between the affinities of the glucose transporter and hexok inase for intracellular glucose. The calculated intraglycosomal metabo lite concentrations demonstrated that enzymes that have been shown to be near-equilibrium in the cytosol must work far from equilibrium in t he glycosome in order to maintain the high glycolytic flux in the latt er.