Can yeast glycolysis be understood in terms of <i>in vitro</i> kinetics of the constituent enzymes? Testing biochemistry

Teusink, Bas; Passarge, J.; Reijenga, C.A.; Esgalhado, Eugenia; Weijden, Coen C. van der; Schepper, Mike; Walsh, Margaret E.; Bakker, Barbara M.; Dam, K. Van; Westerhoff, Hans V.; Snoep, Jacky L.

doi:10.1046/j.1432-1327.2000.01527.x

Cited by 620 publications

(763 citation statements)

References 121 publications

Supporting

Mentioning

733

Contrasting

Unclassified

Order By: Relevance

“…Here two problems arise. First, it was found that in vitro kinetics do not reflect in vivo kinetics [19]. Second, for many enzymes in vitro kinetics are not available.…”

Section: Metabolic Reaction Network Models To Redesign Organisms: Redmentioning

confidence: 99%

Impact of Thermodynamic Principles in Systems Biology

Heijnen

2010

Biosystems Engineering II

View full text Add to dashboard Cite

show abstract

“…Here two problems arise. First, it was found that in vitro kinetics do not reflect in vivo kinetics [19]. Second, for many enzymes in vitro kinetics are not available.…”

Section: Metabolic Reaction Network Models To Redesign Organisms: Redmentioning

confidence: 99%

Impact of Thermodynamic Principles in Systems Biology

Heijnen

2010

Biosystems Engineering II

View full text Add to dashboard Cite

show abstract

“…When a number of enzymatic reactions interplay, based on enzymatic kinetics it has been shown that establishment of a stable state requires specific constraints on kinetic parameters, particularly maximal reaction activities [16,17,31,32]. In order to obtain a stable steady state based on the parameters in literature, many of the parameters need to be adjusted [33,34]. The constraints for formation of stable states in many interplaying enzymes are kinetic constraints for a biological network [17].…”

Section: Discussionmentioning

confidence: 99%

Dissipation and maintenance of stable states in an enzymatic system: Analysis and simulation

Liu¹

2006

Biophysical Chemistry

View full text Add to dashboard Cite

Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThe constraint-based analysis has emerged as a useful tool for analysis of biochemical networks.An essential assumption for constraint-based analysis is the formation of a stable steady state.This work investigates dissipation and maintenance of stable states in a simple reversible enzymatic reaction with substrate inhibition. Under mass-action kinetics, the conditions under which the reaction maintains a stable steady state are analytically derived and numerically confirmed. It is shown that, in order to maintain a steady state in the regulated reaction, maximal enzyme activity must be much higher than input rate. Moreover, it is revealed that requirements for large enzyme activity are due to substrate inhibition. It is suggested that high activities of enzymes may play a vital role in protecting a stable state from its catastrophic collapse, giving an additional explanation to an intriguing problem -why the activities of some enzymes greatly exceed the flux capacity of a pathway. In addition, dissipation of the enzymatic reaction is analysed. It is shown that collapse of stable states is always associated with a point at which dissipation is the highest. Therefore, in order to maintain a stable state, dissipation of the reaction must be less than a critical value. Moreover, although external forcing may not change net mass flow, it may lead to collapse of stable states. Furthermore, when stable states collapse at a critical forcing amplitude and period, dissipation also reaches a highest value. It is concluded that collapse of stable steady state in the enzyme system with substrate inhibition always corresponds to critical points at which dissipation is highest, regardless if the reaction is forced or not.Therefore, for the substrate inhibited reaction, maintenance of stable states is intrinsically related to level of dissipation.3

show abstract

“…In case of estimating dynamic fluxes given an assumed objective, the results are compared with flux estimations based on concentration measurements in time and 13 C mass isotopomer measurements. In contrast to 13 C MFA, our method only uses metabolite concentration measurements (and not 13 C mass isotopomer measurements) to estimate the fluxes.…”

Section: Methodsmentioning

confidence: 99%

“…In contrast to 13 C MFA, our method only uses metabolite concentration measurements (and not 13 C mass isotopomer measurements) to estimate the fluxes.…”

Section: Methodsmentioning

confidence: 99%

“…24 In this paper we present our method (MetDFBA) and underlying mathematical framework to determine flux changes after perturbation of a biological system. We first demonstrate the validity of our method by comparing our results to flux estimations based on dynamic 13 C experiments, which we consider as a experimental reference. For these estimations time-resolved metabolomics data from a feastfamine experiment with Penicillium chrysogenum was used.…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

MetDFBA: incorporating time-resolved metabolomics measurements into dynamic flux balance analysis

et al. 2015

Self Cite

View full text Add to dashboard Cite

. (2015). MetDFBA: incorporating time-resolved metabolomics measurements into dynamic flux balance analysis. Molecular BioSystems, 11(1), 137-145. DOI: 10.1039/c4mb00510d General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Understanding cellular adaptation to environmental changes is one of the major challenges in systems biology. To understand how cellular systems react towards perturbations of their steady state, the metabolic dynamics have to be described. Dynamic properties can be studied with kinetic models but development of such models is hampered by limited in vivo information, especially kinetic parameters.Therefore, there is a need for mathematical frameworks that use a minimal amount of kinetic information. One of these frameworks is dynamic flux balance analysis (DFBA), a method based on the assumption that cellular metabolism has evolved towards optimal changes to perturbations. However, DFBA has some limitations. It is less suitable for larger systems because of the high number of parameters to estimate and the computational complexity. In this paper, we propose MetDFBA, a modification of DFBA, that incorporates measured time series of both intracellular and extracellular metabolite concentrations, in order to reduce both the number of parameters to estimate and the computational complexity. MetDFBA can be used to estimate dynamic flux profiles and, in addition, test hypotheses about metabolic regulation. In a first case study, we demonstrate the validity of our method by comparing our results to flux estimations based on dynamic 13 C MFA measurements, which we considered as experimental reference. For these estimations time-resolved metabolomics data from a feast-famine experiment with Penicillium chrysogenum was used. In a second case study, we used time-resolved metabolomics data from glucose pulse experiments during aerobic growth of Saccharomyces cerevisiae to test various metabolic objectives.

show abstract

Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry

Cited by 620 publications

References 121 publications

Impact of Thermodynamic Principles in Systems Biology

Impact of Thermodynamic Principles in Systems Biology

Dissipation and maintenance of stable states in an enzymatic system: Analysis and simulation

MetDFBA: incorporating time-resolved metabolomics measurements into dynamic flux balance analysis

Contact Info

Product

Resources

About