Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 226, Issue 3, Pages 265-291Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2003.08.010
Keywords
biochemical systems theory; generalized mass action system; metabolic pathway analysis; signal transduction; sphingolipid metabolism; S-system
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Funding
- NIGMS NIH HHS [1 R01 GM63265] Funding Source: Medline
- NLM NIH HHS [T15 LM07438] Funding Source: Medline
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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. (C) 2003 Published by Elsevier Ltd.
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