engleski

Probabilistic Metabolic Control Analysis

Applied is the probabilistic analysis of metabolic control of E. coli central metabolism upon glucose impulse. It is based on experimental data of intracellular metabolite meas-urements during the 15 seconds of the impulse imposed after glucose starvation and the kinetic model developed fitting of metabolite and cofactor transients to the model pre-dictions.1, 2 The probabilistic analysis is based on numerical simulation and evaluation of the multidimensional variances of the metabolic fluxes due to stochastic variations of the input flux and the model parameters. The system parameters are assumed to be in-dependent random variables with uniform probability density functions in the range of 1 order of magnitude around the estimated optimal values. The system parameter space is filled and sampled by Lissajou curves enabling association between system variables and discrete frequencies enabling the variance evaluation by Fourirer amplitude sensi-tivities. The analysis indicates which are the key enzymes and enzyme-metabolite-cofactor interactions during the adaptation of the central metabolism to the impulse. For example, it reveals a very strong shift in the range of the several orders of magnitude of the metabolic control of glucose intake from phosphotransferase (PTS) system to phos-phofructokinase (PFK) which occurs within the first second of the impulse. Similarly, observed are the transients in control of the flux of phosphoenolpyruvate to pyruvate in which the initial control of pyruvat kinase is shifted to the tandem PTS and PFK. For number of fluxes, such as pyruvate to biomass, is exhibited simultaneous concentrated control of number of enzyme throughout the impulse period. The results are compared with the results of the infinitesimal fixed point metabolic control analysis and discussed are implications for possible design of synthetic pathways.

metabic flux analysis; probability; biotechnology

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