TY  - JOUR
A1  - Steuer, Ralf
A1  - Gross, Thilo
A1  - Selbig, Joachim
A1  - Blasius, Bernd
T1  - Structural kinetic modeling of metabolic networks
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - To develop and investigate detailed mathematical models of metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, kinetic modeling is still often severely hampered by inadequate knowledge of the enzyme-kinetic rate laws and their associated parameter values. Here we propose a method that aims to give a quantitative account of the dynamical capabilities of a metabolic system, without requiring any explicit information about the functional form of the rate equations. Our approach is based on constructing a local linear model at each point in parameter space, such that each element of the model is either directly experimentally accessible or amenable to a straightforward biochemical interpretation. This ensemble of local linear models, encompassing all possible explicit kinetic models, then allows for a statistical exploration of the comprehensive parameter space. The method is exemplified on two paradigmatic metabolic systems: the glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.
KW  - systems biology
KW  - computational biochemistry
KW  - metabolomics
KW  - metabolic regulation
KW  - biological robustness
Y1  - 2006
U6  - https://doi.org/10.1073/pnas.0600013103
SN  - 0027-8424
SN  - 1091-6490
VL  - 103
IS  - 32
SP  - 11868
EP  - 11873
PB  - National Academy of Sciences
CY  - Washington
ER  -