Abstract
Mathematical models are key to systems biology where they typically describe the topology and dynamics of biological networks, listing biochemical entities and their relationships with one another. Some (hyper)thermophilic Archaea contain an enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate omitting adenosine 5′-triphosphate (ATP) formation by substrate-level-phosphorylation via phosphoglycerate kinase. In this study we formulate three hypotheses that could explain functionally why GAPN exists in these Archaea, and then construct and use mathematical models to test these three hypotheses. We used kinetic parameters of enzymes of Sulfolobus solfataricus (S. solfataricus) which is a thermo-acidophilic archaeon that grows optimally between 60 and 90 °C and between pH 2 and 4. For comparison, we used a model of Saccharomyces cerevisiae (S. cerevisiae), an organism that can live at moderate temperatures. We find that both the first hypothesis, i.e., that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plus phosphoglycerate kinase (PGK) route (the alternative to GAPN) is thermodynamically too much uphill and the third hypothesis, i.e., that GAPDH plus PGK are required to carry the flux in the gluconeogenic direction, are correct. The second hypothesis, i.e., that the GAPDH plus PGK route delivers less than the 1 ATP per pyruvate that is delivered by the GAPN route, is only correct when GAPDH reaction has a high rate and 1,3-bis-phosphoglycerate (BPG) spontaneously degrades to 3PG at a high rate.
Original language | English |
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Article number | 876 |
Journal | International Journal of Molecular Sciences |
Volume | 18 |
Issue number | 4 |
DOIs | |
Publication status | Published - 20 Apr 2017 |
Funding
The modeling was used the Infrastructure Systems Biology Europe M4 modeling service (www.ISBE.NL) and was supported by the University of Amsterdam RPS Systems Biology as well as by various systems biology grants, zoals Synpol: EU-FP7 (KBBE.2012.3.4-02 #311815), Corbel: EU-H2020 (NFRADEV-4-2014-2015 #654248), Epipredict: EU-H2020 MSCA-ITN-2014-ETN: Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN) #642691, BBSRC China: BB/J020060/1. Yanfei Zhang thanks the China Scholarship Council for a PhD fellowship. Matteo Barberis thanks the SILS Starting Grant of the University of Amsterdam (UvA). No funds were received to publish open access. This work was performed within the e:Bio initiative of the Federal Ministry of Education and Research (BMBF), Germany. Theresa Kouril and Bettina Siebers acknowledge the BMBF for financial support (SulfoSYSBIOTEC 0316188A, HotSysAPP 031L0078A). The authors acknowledge Thierry Mondeel who helps Yanfei Zhang to construct the models and Stefania Astrologo who helps in preparing the figure that summarizes the manuscript.
Funders | Funder number |
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EU-H2020 | MSCA-ITN-2014-ETN |
Horizon 2020 Framework Programme | 642691, 654248 |
Biotechnology and Biological Sciences Research Council | BB/J020060/1 |
Universiteit van Amsterdam | |
Bundesministerium für Bildung und Forschung | HotSysAPP 031L0078A, 0316188A |
China Scholarship Council | |
Seventh Framework Programme | 311815 |
Keywords
- Archaea
- Flux
- Flux control coefficient
- GAPN
- Mathematical models
- Non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase