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Microscopic Kinetics Modeling Framework for Oxidoreductase Catalyzed Bioenergetic Reactions

Ivan Chang, Pierre Baldi

We introduce a new unifying kinetic framework based on a set of universal properties of oxidoreductases (EC 1) applicable to both macroscopic steady-state velocity equation and microscopic system of elementary internal reaction approaches. The framework not only provides a good complement between the two modeling approaches, but could also be reduced logically and programmatically to specific sub-mechanisms, thus enabling a common standard to which the various models can be compared. To facilitate the application of the framework, we present RedoxMech: a new language extension of the xCellerator reaction modeling software based in Mathematica that allows easier creation of EC 1 model from its complex mathematical formalism. Through RedoxMech, we show how the framework enables one to extract unitary rate constants from steady-state kinetic experiments, and conversely incorporate micro domain properties unto the equivalent macro domain rate equations. In particular, we demonstrate how one could acquire the statistical moments that characterize the variations intrinsic to the oxidoreductase reaction through stochastic simulations and ascribe them on the macro steady-state velocity equation that are typically better suited for integration into higher scale reaction models.

Documents for Download:
xCellerator MathematicaTM Modeling Package: xCellerator
RedoxMech xCellerator Extension Package: RedoxMech.m
RedoxMech MathematicaTM Demonstration Notebook: RedoxMech.nb

Experimental Data for Download:
Raw enzyme kinetics data of rat muscle mitochondria complex I: ComplexI_121207.zip
Raw enzyme kinetics data of mouse heart mitochondria complex III: ComplexIII_25062009.zip

RedoxMech.m installation tip:
Under the File menu in MathematicaTM, select "Install..." option and then specify "Package" as the "Type of Item to Install" and select "From File" (choose the location of the download RedoxMech.m file) as the "Source".