Integration of kinetic information on yeast sphingolipid metabolism in dynamical pathway models

For the first time, kinetic information from the literature was collected and used to construct integrative dynamical mathematical models of sphingolipid metabolism. One model was designed primarily with kinetic equations in the tradition of Michaelis and Menten whereas the other two models were des...

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Bibliographic Details
Published in:Journal of theoretical biology 2004-02, Vol.226 (3), p.265-291
Main Authors: Alvarez-Vasquez, Fernando, Sims, Kellie J., Hannun, Yusuf A., Voit, Eberhard O.
Format: Article
Language:English
Subjects:
Biochemical systems theory
Generalized mass action system
Metabolic pathway analysis
Models, Biological
S-system
Saccharomyces cerevisiae - metabolism
Signal transduction
Signal Transduction - physiology
Sphingolipid metabolism
sphingolipids
Sphingolipids - metabolism
Systems Theory
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Summary:For the first time, kinetic information from the literature was collected and used to construct integrative dynamical mathematical models of sphingolipid metabolism. One model was designed primarily with kinetic equations in the tradition of Michaelis and Menten whereas the other two models were designed as alternative power-law models within the framework of Biochemical Systems Theory. Each model contains about 50 variables, about a quarter of which are dependent (state) variables, while the others are independent inputs and enzyme activities that are considered constant. The models account for known regulatory signals that exert control over the pathway. Standard mathematical testing, repeated revisiting of the literature, and numerous rounds of amendments and refinements resulted in models that are stable and rather insensitive to perturbations in inputs or parameter values. The models also appear to be compatible with the modest amount of experimental experience that lends itself to direct comparisons. Even though the three models are based on different mathematical representations, they show dynamic responses to a variety of perturbations and changes in conditions that are essentially equivalent for small perturbations and similar for large perturbations. The kinetic information used for model construction and the models themselves can serve as a starting point for future analyses and refinements.
ISSN:0022-5193
1095-8541
DOI:10.1016/j.jtbi.2003.08.010