Explicit consideration of topological and parameter uncertainty gives new insights into a well-established model of glycolysis

Achcar, F. , Barrett, M.P. and Breitling, R. (2013) Explicit consideration of topological and parameter uncertainty gives new insights into a well-established model of glycolysis. FEBS Journal, 280(18), pp. 4640-4651. (doi:10.1111/febs.12436) (PMID:23865459) (PMCID:PMC4768353)

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Abstract

Previous models of glycolysis in the sleeping sickness parasite Trypanosoma brucei assumed that the core part of glycolysis in this unicellular parasite is tightly compartimentalized within an organelle, the glycosome, which had previously been shown to contain most of the glycolytic enzymes. The glycosomes were assumed to be largely impermeable, and exchange of metabolites between the cytosol and the glycosome was assumed to be regulated by specific transporters in the glycosomal membrane. This tight compartmentalization was considered to be essential for parasite viability. Recently, size-specific metabolite pores were discovered in the membrane of glycosomes. These channels are proposed to allow smaller metabolites to diffuse across the membrane but not larger ones. In light of this new finding, we re-analyzed the model taking into account uncertainty about the topology of the metabolic system in T. brucei, as well as uncertainty about the values of all parameters of individual enzymatic reactions. Our analysis shows that these newly-discovered nonspecific pores are not necessarily incompatible with our current knowledge of the glycosomal metabolic system, provided that the known cytosolic activities of the glycosomal enzymes play an important role in the regulation of glycolytic fluxes and the concentration of metabolic intermediates of the pathway.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Achcar, Dr Fiona and Breitling, Professor Rainer and Barrett, Professor Michael
Authors: Achcar, F., Barrett, M.P., and Breitling, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:FEBS Journal
Publisher:Wiley
ISSN:1742-464X
ISSN (Online):1742-4658
Published Online:19 August 2013
Copyright Holders:Copyright © 2016 Wiley
First Published:First published in FEBS Journal 280(18):4640-4651
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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