2012.6: Letting the flux define the kinetics: using a single steady state to predict network behaviour under diverse stress conditions
2012.6: Natalie J. Stanford, Kieran Smallbone and Pedro Mendes (2012) Letting the flux define the kinetics: using a single steady state to predict network behaviour under diverse stress conditions.
Full text available as:
|PDF - Archive staff only - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader|
Motivation The understanding of metabolic interactions has grown rapidly in recent years with metabolic network reconstructions constantly increasing in scope and quality. These networks can be manipulated into models which allow for fluxes to be estimated using methods such as flux balance analysis. However, the solution space of fluxes is large, and the inability to provide dynamic behaviour of the system can make understanding it under changing conditions difficult. It is under these circumstances where kinetic models can prove more valuable. However, collecting kinetic information for large scale networks is time consuming and expensive, and existing data is difficult to find and collate.
Results We develop and validate a novel methodology which uses the flux information of one steady state to define the kinetics of the system and produce a reasonable approximation of the steady state behaviour of the real system. We show that first approximation models, in the first instance, show a poor ability to extrapolate beyond the initial conditions. However, metabolic control analysis directs our attention towards the most important reactions of the network. When experimentally-elucidated kinetics are used for those reactions, and the remainder of the network modelled using empirical rate laws that are inspired in enzyme kinetics, predictability improves dramatically.
|Item Type:||MIMS Preprint|
|Subjects:||MSC 2000 > 92 Biology and other natural sciences|
|Deposited By:||Dr Kieran Smallbone|
|Deposited On:||05 January 2012|