Bakker B M, Michels P A, Opperdoes F R, Westerhoff H V
Microbial Physiology, BioCentrum Amsterdam, Vrije Universiteit, De Boelelaan 1087, NL-1081 HV Amsterdam, BioCentrum Amsterdam, University of Amsterdam, Plantage Muidergracht 12, NL-1018 TV Amsterdam, The Netherlands.
J Biol Chem. 1997 Feb 7;272(6):3207-15. doi: 10.1074/jbc.272.6.3207.
In trypanosomes the first part of glycolysis takes place in specialized 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 organism is developed on the basis of all available kinetic data. The fluxes and the cytosolic metabolite concentrations as predicted by the model 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 glycerol, although the amount of glycerol needed to inhibit glycolysis completely was lower than experimentally determined. At low extracellular glucose concentrations the intracellular glucose concentration remained very low, and only at 5 mM of extracellular glucose, free glucose started to accumulate intracellularly, in close agreement with experimental observations. This biphasic relation could be related to the large difference between the affinities of the glucose transporter and hexokinase for intracellular glucose. The calculated intraglycosomal metabolite concentrations demonstrated that enzymes that have been shown to be near-equilibrium in the cytosol must work far from equilibrium in the glycosome in order to maintain the high glycolytic flux in the latter.
在锥虫中,糖酵解的第一阶段发生在特殊的微体即糖体中。布氏锥虫的大多数糖酵解酶已被纯化并进行了动力学表征。本文基于所有可用的动力学数据,建立了该生物体血流形式下糖酵解的数学模型。该模型预测的通量和胞质代谢物浓度与在非生长锥虫中测得的可用数据一致,无论是在有氧还是无氧条件下。该模型还重现了甘油对无氧糖酵解的抑制作用,尽管完全抑制糖酵解所需的甘油量低于实验测定值。在低细胞外葡萄糖浓度下,细胞内葡萄糖浓度仍然很低,只有在细胞外葡萄糖浓度为5 mM时,游离葡萄糖才开始在细胞内积累,这与实验观察结果密切一致。这种双相关系可能与葡萄糖转运体和己糖激酶对细胞内葡萄糖亲和力的巨大差异有关。计算得出的糖体内代谢物浓度表明,已证明在胞质溶胶中接近平衡的酶在糖体中必须远离平衡工作,以维持后者中的高糖酵解通量。