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Bidirectionality and Compartmentation of Metabolic Fluxes Are Revealed in the Dynamics of Isotopomer Networks
Laboratory of Systems Biology, Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618 Tallinn, Estonia
Department of Food Processing, Tallinn University of Technology, Ehitajate 5, 19086 Tallinn, Estonia
* Author to whom correspondence should be addressed.
Received: 11 March 2009; in revised form: 7 April 2009 / Accepted: 14 April 2009 / Published: 17 April 2009
Abstract: Isotope labeling is one of the few methods of revealing the in vivo bidirectionality and compartmentalization of metabolic fluxes within metabolic networks. We argue that a shift from steady state to dynamic isotopomer analysis is required to deal with these cellular complexities and provide a review of dynamic studies of compartmentalized energy fluxes in eukaryotic cells including cardiac muscle, plants, and astrocytes. Knowledge of complex metabolic behaviour on a molecular level is prerequisite for the intelligent design of genetically modified organisms able to realize their potential of revolutionizing food, energy, and pharmaceutical production. We describe techniques to explore the bidirectionality and compartmentalization of metabolic fluxes using information contained in the isotopic transient, and discuss the integration of kinetic models with MFA. The flux parameters of an example metabolic network were optimized to examine the compartmentalization of metabolites and and the bidirectionality of fluxes in the TCA cycle of Saccharomyces uvarum for steady-state respiratory growth.
Keywords: Metabolic network; isotopomer dynamics; MFA; mathematical modeling; compartmentalization; ¹³C NMR
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MDPI and ACS Style
Schryer, D.W.; Peterson, P.; Paalme, T.; Vendelin, M. Bidirectionality and Compartmentation of Metabolic Fluxes Are Revealed in the Dynamics of Isotopomer Networks. Int. J. Mol. Sci. 2009, 10, 1697-1718.
Schryer DW, Peterson P, Paalme T, Vendelin M. Bidirectionality and Compartmentation of Metabolic Fluxes Are Revealed in the Dynamics of Isotopomer Networks. International Journal of Molecular Sciences. 2009; 10(4):1697-1718.
Schryer, David W.; Peterson, Pearu; Paalme, Toomas; Vendelin, Marko. 2009. "Bidirectionality and Compartmentation of Metabolic Fluxes Are Revealed in the Dynamics of Isotopomer Networks." Int. J. Mol. Sci. 10, no. 4: 1697-1718.