From steady-state to synchronized yeast glycolytic oscillations II: model validation.
In an accompanying paper [du Preez et al., (2012) FEBS J279, 2810-2822], 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.


METHODS
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.
Triple J Group for Molecular Cell Physiology, Department of Biochemistry, Stellenbosch University, Matieland, South Africa.
Franco B
FB
du Preez
David D
DD
van Niekerk
Jacky L
JL
Snoep
D000079:Acetaldehyde / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002474:Cell-Free System / Q000502:physiology; D003486:Cyanides / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007700:Kinetics; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D049490:Systems Biology
D003486:Cyanides; D009243:NAD; D000255:Adenosine Triphosphate; D000079:Acetaldehyde; D005947:Glucose