Sensitivity analysis of metabolic systems /
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| Other Authors: | , , , |
| Format: | Thesis Book |
| Language: | English |
| Published: |
1993.
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| Subjects: | |
| Online Access: | ProQuest, Abstract Link to OAKTrust copy |
| Abstract: | This work presents a new methodology for evaluating the sensitivity of metabolic systems using transient data. We built this method based on Metabolic Control Analysis, which provides a rigorous mathematical basis for the quantitative description of metabolic regulation. We focused on determining of the flux and metabolite concentration control coefficients. These coefficients provide a set of sensitivity indices that one can use to elucidate relevant regulatory features of a metabolic system. Metabolic regulations do not allow arbitrary changes in the intracellular intermediates and place constraints on the system 's response to environmental, genetic, or other perturbations. We derived equations that relate the transient responses of the system with the flux and metabolite concentration control coefficients and developed a method for identifying these coefficients. The equations are valid for systems that possess asymptotically stable steady or quasi-steady states, have reaction kinetics that depend linearly on the variables, and have full rank stoichiometry. We showed that these assumptions are not very restrictive and developed tests to verify their validity. We generalized the identification procedure to include constraints that arise from other chemical, physical, and kinetic laws that govern the system. Some of these constraints also provide regulatory information, such as individualization of non-controlling steps and fast-equilibrium enzymes. We used these constraints to apply criteria to lump complex reaction networks. To test the applicability of the methodology in experimental systems, we used an in vitro partial glycolytic pathway and determined the flux control coefficients of all the enzymes of the pathway. Results showed that the method correctly estimated the flux control coefficients, which we verified using enzyme titration. We also discussed how to apply the methodology to the analysis of continuous reaction systems. One can analyze reaction systems in tubular reactors by varying feed flow rates, and one can perform similar analyses in continuously stirred tank reactors by modifying the stoichiometry. |
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| Item Description: | Vita. "Major subject: Chemical Engineering." |
| Physical Description: | xvi, 183 leaves : illustrations ; 28 cm |
| Bibliography: | Includes bibliographical references. |