Detailed kinetic model of yeast glycolytic oscillation - I

An existing detailed kinetic model for the steady-state behavior of yeast glycolysis was tested for its ability to simulate dynamic behavior. This model (dupreez1) is the basis kinetic model derived from that published by Teusink et al., 2000 (PMID: 10951190).

Creators: Franco du Preez, David D van Niekerk

Submitter: Franco du Preez

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From steady-state to synchronized yeast glycolytic oscillations I: model construction

Abstract (Expand)

An existing detailed kinetic model for the steady-state behavior of yeast glycolysis was tested for its ability to simulate dynamic behavior. Using a small subset of experimental data, the original … model was adapted by adjusting its parameter values in three optimization steps. Only small adaptations to the original model were required for realistic simulation of experimental data for limit-cycle oscillations. The greatest changes were required for parameter values for the phosphofructokinase reaction. The importance of ATP for the oscillatory mechanism and NAD(H) for inter-and intra-cellular communications and synchronization was evident in the optimization steps and simulation experiments. In an accompanying paper [du Preez F et al. (2012) FEBS J doi:10.1111/j.1742-4658.2012.08658.x], we validate the model for a wide variety of experiments on oscillatory yeast cells. The results are important for re-use of detailed kinetic models in modular modeling approaches and for approaches such as that used in the Silicon Cell initiative. Database The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: , David D van Niekerk, Bob Kooi, Johann M Rohwer,

Date Published: 21st Jun 2012

Publication Type: Not specified

From steady-state to synchronized yeast glycolytic oscillations II: model validation

Abstract (Expand)

In an accompanying paper [du Preez et al., (2012) FEBS J doi: 10.1111/j.1742-4658.2012.08665.x], we adapt an existing kinetic model for steady-state yeast glycolysis to simulate limit-cycle oscillations. … Here we validate the model by testing its capacity to simulate a wide range of experiments on dynamics of yeast glycolysis. In addition to its description of the oscillations of glycolytic intermediates in intact cells and the rapid synchronization observed when mixing out-of-phase oscillatory cell populations (see accompanying paper), the model was able to predict the Hopf bifurcation diagram with glucose as the bifurcation parameter (and one of the bifurcation points with cyanide as the bifurcation parameter), the glucose- and acetaldehyde-driven forced oscillations, glucose and acetaldehyde quenching, and cell-free extract oscillations (including complex oscillations and mixed-mode oscillations). Thus, the model was compliant, at least qualitatively, with the majority of available experimental data for glycolytic oscillations in yeast. To our knowledge, this is the first time that a model for yeast glycolysis has been tested against such a wide variety of independent data sets. Database The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: , David D van Niekerk,

Date Published: 13th Jun 2012

Publication Type: Not specified

Sustained glycolytic oscillations in individual isolated yeast cells

Abstract (Expand)

Yeast glycolytic oscillations have been studied since the 1950s in cell-free extracts and intact cells. For intact cells, sustained oscillations have so far only been observed at the population level, … i.e. for synchronized cultures at high biomass concentrations. Using optical tweezers to position yeast cells in a microfluidic chamber, we were able to observe sustained oscillations in individual isolated cells. Using a detailed kinetic model for the cellular reactions, we simulated the heterogeneity in the response of the individual cells, assuming small differences in a single internal parameter. This is the first time that sustained limit-cycle oscillations have been demonstrated in isolated yeast cells. Database The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/gustavsson/index.html free of charge.

Authors: Anna-Karin Gustavsson, David D van Niekerk, Caroline B Adiels, , Mattias Goksör,

Date Published: 23rd May 2012

Publication Type: Not specified

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