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Modeling diauxic glycolytic oscillations in yeast.

ABSTRACT: Glycolytic oscillations in a stirred suspension of starved yeast cells is an excellent model system for studying the dynamics of metabolic switching in living systems. In an open-flow system the oscillations can be maintained indefinitely at a constant operating point where they can be characterized quantitatively by experimental quenching and bifurcation analysis. In this article, we use these methods to show that the dynamics of oscillations in a closed system is a simple transient version of the open-system dynamics. Thus, easy-setup closed-system experiments are also useful for investigations of central metabolism dynamics of yeast cells. We have previously proposed a model for the open system comprised of the primary fermentative reactions in yeast that quantitatively describes the oscillatory dynamics. However, this model fails to describe the transient behavior of metabolic switching in a closed-system experiment by feeding the yeast suspension with a glucose pulse-notably the initial NADH spike and final NADH rise. Another object of this study is to gain insight into the secondary low-flux metabolic pathways by feeding starved yeast cells with various metabolites. Experimental and computational results strongly suggest that regulation of acetaldehyde explains the observed behavior. We have extended the original model with regulation of pyruvate decarboxylase, a reversible alcohol dehydrogenase, and drainage of pyruvate. Using the method of time rescaling in the extended model, the description of the transient closed-system experiments is significantly improved.

SUBMITTER: Hald BO

PROVIDER: S-EPMC2980702 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Modeling diauxic glycolytic oscillations in yeast.

Hald Bjørn Olav BO Sørensen Preben G PG

Biophysical journal 20101101 10

Glycolytic oscillations in a stirred suspension of starved yeast cells is an excellent model system for studying the dynamics of metabolic switching in living systems. In an open-flow system the oscillations can be maintained indefinitely at a constant operating point where they can be characterized quantitatively by experimental quenching and bifurcation analysis. In this article, we use these methods to show that the dynamics of oscillations in a closed system is a simple transient version of ...[more]

PMID: 21081066

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Project description:On the basis of a detailed model of yeast glycolysis, the effect of intercellular dynamics is analysed theoretically. The model includes the main steps of anaerobic glycolysis, and the production of ethanol and glycerol. Transmembrane diffusion of acetaldehyde is included, since it has been hypothesized that this substance mediates the interaction. Depending on the kinetic parameter, the single-cell model shows both stationary and oscillatory behaviour. This agrees with experimental data with respect to metabolite concentrations and phase shifts. The inclusion of intercellular coupling leads to a variety of dynamical modes, such as synchronous oscillations, and different kinds of asynchronous behavior. These oscillations can co-exist, leading to bi- and tri-rhythmicity. The corresponding parameter regions have been identified by a bifurcation analysis. The oscillatory dynamics of synchronized cell populations are investigated by calculating the phase responses to acetaldehyde pulses. Simulations are performed with respect to the synchronization of two subpopulations that are oscillating out of phase before mixing. The effect of the various process on synchronization is characterized quantitatively. While continuous exchange of acetaldehyde might synchronize the oscillations for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulator feedback plays a role in the acceleration of the synchronization. for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulator feedback plays a role in the acceleration of the synchronization.

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Modeling diauxic glycolytic oscillations in yeast.

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Modeling diauxic glycolytic oscillations in yeast.

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