Reference : Quantitative Assignment of Reaction Directionality in a Multicompartmental Human Meta...
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Quantitative Assignment of Reaction Directionality in a Multicompartmental Human Metabolic Reconstruction
Haraldsdottir, Hulda mailto []
Thiele, Ines mailto []
Fleming, Ronan MT mailto []
Biophysical Journal
Biophysical Society
Yes (verified by ORBilu)
[en] Body Temperature ; Genomics ; Humans ; Hydrogen-Ion Concentration ; Metabolic Networks and Pathways ; Models, Biological ; Static Electricity ; Thermodynamics
[en] Reaction directionality is a key constraint in the modeling of genome-scale metabolic networks. We thermodynamically constrained reaction directionality in a multicompartmental genome-scale model of human metabolism, Recon 1, by calculating, in vivo, standard transformed reaction Gibbs energy as a function of compartment-specific pH, electrical potential, and ionic strength. We show that compartmental pH is an important determinant of thermodynamically determined reaction directionality. The effects of pH on transport reaction thermodynamics are only seen to their full extent when metabolites are represented as pseudoisomer groups of multiple protonated species. We accurately predict the irreversibility of 387 reactions, with detailed propagation of uncertainty in input data, and manually curate the literature to resolve conflicting directionality assignments. In at least half of all cases, a prediction of a reversible reaction directionality is due to the paucity of compartment-specific quantitative metabolomic data, with remaining cases due to uncertainty in estimation of standard reaction Gibbs energy. This study points to the pressing need for 1), quantitative metabolomic data, and 2), experimental measurement of thermochemical properties for human metabolites.
Luxembourg Centre for Systems Biomedicine (LCSB): Systems Biochemistry (Fleming Group)
Copyright (c) 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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