engleski

Statistical Metabolic Control Analysis

This work introduces the concept of global sensitivity based on simultaneous variation of a complete set of enzymes, metabolite concentrations, and cofactors in finite ranges of concentrations. Perturbations are defined by finite ranges of concentrations and corresponding probability density distributions. Effects of perturbations of the homeostatic state variables including input and output products of a considered flux, and cofactors on the flux analysis are evaluated. The flux sensitivities are determined as first and second order relative multidimensional variances. The first order effects are reflection of random perturbation of each individual en-zyme, metabolite and cofactor. The dispersions of fluxes due to each perturbation are evaluated by numerical simulation and the Fourier Amplitude Sensitivity Test algorithm. The implications of the proposed theory are demonstrated by computer simulation of theoretical problem on regulation of branched metabolism pathway at steady state, and also unsteady control flux analysis based on experimental data of E. coli central metabolism upon perturbation by glucose impulse.

metabolic control analysis; global sensitivity; FAST

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