title: Phosphoglycerate mutases function as reverse regulated isoenzymes in Synechococcus elongatus PCC 7942.
abstract: Phosphoglycerate-mutase (PGM) is an ubiquitous glycolytic enzyme, which in eukaryotic cells can be found in different compartments. In prokaryotic cells, several PGMs are annotated/localized in one compartment. The identification and functional characterization of PGMs in prokaryotes is therefore important for better understanding of metabolic regulation. Here we introduce a method, based on a multi-level kinetic model of the primary carbon metabolism in cyanobacterium Synechococcus elongatus PCC 7942, that allows the identification of a specific function for a particular PGM. The strategy employs multiple parameter estimation runs in high CO2, combined with simulations testing a broad range of kinetic parameters against the changes in transcript levels of annotated PGMs. Simulations are evaluated for a match in metabolic level in low CO2, to reveal trends that can be linked to the function of a particular PGM. A one-isoenzyme scenario shows that PGM2 is a major regulator of glycolysis, while PGM1 and PGM4 make the system robust against environmental changes. Strikingly, combining two PGMs with reverse transcriptional regulation allows both features. A conclusion arising from our analysis is that a two-enzyme PGM system is required to regulate the flux between glycolysis and the Calvin-Benson cycle, while an additional PGM increases the robustness of the system.
authors.affiliation: Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany. jiri.jablonsky@gmail.com
authors.forename: Jiri
authors.initials: J
authors.lastname: Jablonsky
authors.forename: Martin
authors.initials: M
authors.lastname: Hagemann
authors.forename: Doreen
authors.initials: D
authors.lastname: Schwarz
authors.forename: Olaf
authors.initials: O
authors.lastname: Wolkenhauer
mesh_terms: D002245:Carbon Dioxide / Q000032:analysis; D016000:Cluster Analysis; D003198:Computer Simulation; D006019:Glycolysis; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D010736:Phosphoglycerate Mutase / Q000378:metabolism*; D010788:Photosynthesis / Q000502:physiology*; D046940:Synechococcus / Q000201:enzymology*; D049490:Systems Biology / Q000379:methods
chemical_list: D007527:Isoenzymes; D002245:Carbon Dioxide; D010736:Phosphoglycerate Mutase