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The peculiar glycolytic pathway in hyperthermophylic archaea: Understanding its whims by experimentation in silico

Zhang, Y., Kouril, T., Snoep, J.L., Siebers, B., Barberis, Matteo and Westerhoff, H.V. (2017) The peculiar glycolytic pathway in hyperthermophylic archaea: Understanding its whims by experimentation in silico International Journal of Molecular Sciences, 18 (4).

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Zhang, Y.
Kouril, T.
Snoep, J.L.
Siebers, B.
Westerhoff, H.V.
Date : 20 April 2017
Funders : European Commission 7th Framework Programme, European Union's Horizon 2020, Biotechnology and Biological Sciences Research Council (BBSRC)
DOI : 10.3390/ijms18040876
Copyright Disclaimer : © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Uncontrolled Keywords : Archaea; Flux; Flux control coefficient; GAPN; Mathematical models; Non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase
Depositing User : Clive Harris
Date Deposited : 12 Apr 2019 13:05
Last Modified : 12 Apr 2019 13:05

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