ArticleThe FEBS journal2013
Explicit consideration of topological and parameter uncertainty gives new insights into a well-established model of glycolysis.
Article in The FEBS journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 17 citations in OpenAlex.
- An adaptableMolecular omics · 2024Article
- The bloodstream form of Trypanosoma brucei displays non-canonical gluconeogenesis.PLoS neglected tropical diseases · 2024Article
- Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei.PLoS pathogens · 2018Article
- Defining informative priors for ensemble modeling in systems biology.Nature protocols · 2018Article
- Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana.PLoS pathogens · 2018Article
- Article
- Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.PLoS pathogens · 2015Article
- The silicon trypanosome: a test case of iterative model extension in systems biology.Advances in microbial physiology · 2014Review
- Handling uncertainty in dynamic models: the pentose phosphate pathway in Trypanosoma brucei.PLoS computational biology · 2013Article
- LC-MS-based absolute metabolite quantification: application to metabolic flux measurement in trypanosomes.Metabolomics : Official journal of the Metabolomic SocietyArticle
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
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.
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