Metabolic control models

It is important that chemical engineers master an understanding of metabolic engineering, which uses genetically modified or selected organisms to manipulate the biochemical pathways in a cell to produce a new product, to eliminate unwanted reactions, or to increase the yield of a desired product. Mathematical models have the potential to enable major advances in metabolic control. An excellent example of industrial application of metabolic engineering is the DuPont process for the conversion of com sugar into 1,3-propanediol,... 

D. Garfinkel and B. Hess, Metabolic control mechanisms. VII. A detailed computer model of... 

P. J. Mulquiney and P. W. Kuchel, Model of 2,3 bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations Computer simulation and metabolic control analysis. Biochem. J. 342 (3), 597 604 (1999). 

J. E. Bailey and V. Hatzimanikatis, Effects of spatiotemporal variations on metabolic control Approximate analysis using (log)linear kinetic models. Biotechnol. Bioeng. (1997). 

Delgado et aL recently demonstrated that time-scale separation is an effective way to localize metabolic control to only a few enzymes. They considered model pathways in which the eigenvalues of the Jacobian of the system are widely separated (i.e., systems with time-scale separation). Their treatment assumes the system possesses a unique, asymptotically stable steady-state and that the reaction steps of the system under analysis are... 

METABOLIC CONTROL ANALYSIS METABOLONS META-MODEL FMN,... 

The symmetry model is useful even if it does oversimplify the situation, because it provides a conceptual framework for discussing the relationships between conformational transitions and the effects of allosteric activators and inhibitors. In the following sections we consider three oligomeric enzymes that are under metabolic control and see that substrates and allosteric effectors do tend to stabilize each of these enzymes in one or the other of two distinctly different conformations. 

This discussion of starvation illustrates the complex problems of interpreting the results of even well controlled experiments on single dietary manipulations. It also shows the difficulties of extrapolating results from one set of environmental conditions to another. Clearly, such extrapolation is hazardous in assessing the contribution of any single dietary factor to large interindividual variations in metabolism of model drugs. Other approaches must be... 

Bottom-up systems biology does not rely that heavily on Omics. It predates top-down systems biology and it developed out of the endeavors associated with the construction of the first mathematical models of metabolism in the 1960s [10, 11], the development of enzyme kinetics [12-15], metabolic control analysis [16, 17], biochemical systems theory [18], nonequilibrium thermodynamics [6, 19, 20], and the pioneering work on emergent aspects of networks by researchers such as Jacob, Monod, and Koshland [21-23]. 

Many methods have been developed for model analysis for instance, bifurcation and stability analysis [88, 89], parameter sensitivity analysis [90], metabolic control analysis [16, 17, 91] and biochemical systems analysis [18]. One highly important method for model analysis and especially for large models, such as many silicon cell models, is model reduction. Model reduction has a long history in the analysis of biochemical reaction networks and in the analysis of nonlinear dynamics (slow and fast manifolds) [92-104]. In all cases, the aim of model reduction is to derive a simplified model from a larger ancestral model that satisfies a number of criteria. In the following sections we describe a relatively new form of model reduction for biochemical reaction networks, such as metabolic, signaling, or genetic networks. 

Garfinkel, D. Hess, B. Metabolic Control mechanisms, vii. A detailed computer model of the glycolytic pathway in ascites cells. J Biol Chem 1964, 239 971-983. 

Martens, D. E. Hugenholtz, J. Kleere-bezem, M. et al. Metabolic engineering of lactic add bacteria, the combined approach kinetic modelling, metabolic control and experimental analysis. Microbiology 2002,148 1003-1013. 

Another two key concepts in metabolic engineering are metabolic pathway analysis and metabolic pathway modeling. The former is used for assessing inherent network properties in the complete biochemical reaction networks. It involves identification of the metabolic network structure (or pathway topology), quantification of the fluxes through the branches of the metabolic network, and identification of the control structures within the metabolic network. 

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