Metabolic control analysis under uncertainty: Framework development and case studies

Information about the enzyme kinetics in a metabolic network will enable understanding of the function of the network and quant. prediction of the network responses to genetic and environmental perturbations. Despite recent advances in exptl. techniques, such information is limited and existing exptl. data show extensive variation and they are based on in vitro expts. In this article, we present a computational framework based on the well-established (log)linear formalism of metabolic control anal. The framework employs a Monte Carlo sampling procedure to simulate the uncertainty in the kinetic data and applies statistical tools for the identification of the rate-limiting steps in metabolic networks. We applied the proposed framework to a branched biosynthetic pathway and the yeast glycolysis pathway. Anal. of the results allowed us to interpret and predict the responses of metabolic networks to genetic and environmental changes, and to gain insights on how uncertainty in the kinetic mechanisms and kinetic parameters propagate into the uncertainty in predicting network responses. Some of the practical applications of the proposed approach include the identification of drug targets for metabolic diseases and the guidance for design strategies in metabolic engineering for the purposeful manipulation of the metab. of industrial organisms. [on SciFinder (R)]

Published in:
Biophysical Journal, 87, 6, 3750-3763
7-8 FIELD Section Title:Enzymes
Department of Chemical and Biological Engineering,Northwestern University,Evanston,IL,USA. FIELD URL:
written in English.

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 Record created 2007-01-11, last modified 2019-03-16

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