Literature DB >> 9013556

Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes.

B M Bakker1, P A Michels, F R Opperdoes, H V Westerhoff.   

Abstract

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.

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Year:  1997        PMID: 9013556     DOI: 10.1074/jbc.272.6.3207

Source DB:  PubMed          Journal:  J Biol Chem        ISSN: 0021-9258            Impact factor:   5.157


  46 in total

1.  Compartmentation protects trypanosomes from the dangerous design of glycolysis.

Authors:  B M Bakker; F I Mensonides; B Teusink; P van Hoek; P A Michels; H V Westerhoff
Journal:  Proc Natl Acad Sci U S A       Date:  2000-02-29       Impact factor: 11.205

2.  Roles of triosephosphate isomerase and aerobic metabolism in Trypanosoma brucei.

Authors:  S Helfert; A M Estévez; B Bakker; P Michels; C Clayton
Journal:  Biochem J       Date:  2001-07-01       Impact factor: 3.857

3.  What it takes to understand and cure a living system: computational systems biology and a systems biology-driven pharmacokinetics-pharmacodynamics platform.

Authors:  Maciej Swat; Szymon M Kiełbasa; Sebastian Polak; Brett Olivier; Frank J Bruggeman; Mark Quinton Tulloch; Jacky L Snoep; Arthur J Verhoeven; Hans V Westerhoff
Journal:  Interface Focus       Date:  2010-12-08       Impact factor: 3.906

Review 4.  Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

Authors:  Barbara M Bakker; Karen van Eunen; Jeroen A L Jeneson; Natal A W van Riel; Frank J Bruggeman; Bas Teusink
Journal:  Biochem Soc Trans       Date:  2010-10       Impact factor: 5.407

5.  Structure-based design of submicromolar, biologically active inhibitors of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase.

Authors:  A M Aronov; S Suresh; F S Buckner; W C Van Voorhis; C L Verlinde; F R Opperdoes; W G Hol; M H Gelb
Journal:  Proc Natl Acad Sci U S A       Date:  1999-04-13       Impact factor: 11.205

6.  Dynamics of muscle glycogenolysis modeled with pH time course computation and pH-dependent reaction equilibria and enzyme kinetics.

Authors:  Kalyan Vinnakota; Melissa L Kemp; Martin J Kushmerick
Journal:  Biophys J       Date:  2006-04-14       Impact factor: 4.033

7.  Simplified modelling of metabolic pathways for flux prediction and optimization: lessons from an in vitro reconstruction of the upper part of glycolysis.

Authors:  Julie B Fiévet; Christine Dillmann; Gilles Curien; Dominique de Vienne
Journal:  Biochem J       Date:  2006-06-01       Impact factor: 3.857

8.  Energy metabolism of bloodstream form Trypanosoma theileri.

Authors:  Jaap J van Hellemond; Aad Hoek; Paul Wichgers Schreur; Vladimir Chupin; Suat Ozdirekcan; Dirk Geysen; Koen W A van Grinsven; Ad P Koets; Peter Van den Bossche; Stanny Geerts; Aloysius G M Tielens
Journal:  Eukaryot Cell       Date:  2007-07-20

9.  In silico Geobacter sulfurreducens metabolism and its representation in reactive transport models.

Authors:  E L King; K Tuncay; P Ortoleva; C Meile
Journal:  Appl Environ Microbiol       Date:  2008-11-14       Impact factor: 4.792

10.  Metabolic control analysis of glycerol synthesis in Saccharomyces cerevisiae.

Authors:  Garth R Cronwright; Johann M Rohwer; Bernard A Prior
Journal:  Appl Environ Microbiol       Date:  2002-09       Impact factor: 4.792

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