A unifying kinetic framework for modeling oxidoreductase-catalyzed reactions

MOTIVATION Oxidoreductases are a fundamental class of enzymes responsible for the catalysis of oxidation-reduction reactions, crucial in most bioenergetic metabolic pathways. From their common root in the ancient prebiotic environment, oxidoreductases have evolved into diverse and elaborate protein structures with specific kinetic properties and mechanisms adapted to their individual functional roles and environmental conditions. While accurate kinetic modeling of oxidoreductases is thus important, current models suffer from limitations to the steady-state domain, lack empirical validation or are too specialized to a single system or set of conditions. RESULTS To address these limitations, we introduce a novel unifying modeling framework for kinetic descriptions of oxidoreductases. The framework is based on a set of seven elementary reactions that (i) form the basis for 69 pairs of enzyme state transitions for encoding various specific microscopic intra-enzyme reaction networks (micro-models), and (ii) lead to various specific macroscopic steady-state kinetic equations (macro-models) via thermodynamic assumptions. Thus, a synergistic bridge between the micro and macro kinetics can be achieved, enabling us to extract unitary rate constants, simulate reaction variance and validate the micro-models using steady-state empirical data. To help facilitate the application of this framework, we make available RedoxMech: a Mathematica™ software package that automates the generation and customization of micro-models. AVAILABILITY The Mathematica™ source code for RedoxMech, the documentation and the experimental datasets are all available from: http://www.igb.uci.edu/tools/sb/metabolic-modeling. CONTACT [email protected] SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.