title: Modeling the respiratory chain complexes with biothermokinetic equations - the case of complex I.
abstract: The mitochondrial respiratory chain plays a crucial role in energy metabolism and its dysfunction is implicated in a wide range of human diseases. In order to understand the global expression of local mutations in the rate of oxygen consumption or in the production of adenosine triphosphate (ATP) it is useful to have a mathematical model in which the changes in a given respiratory complex are properly modeled. Our aim in this paper is to provide thermodynamics respecting and structurally simple equations to represent the kinetics of each isolated complexes which can, assembled in a dynamical system, also simulate the behavior of the respiratory chain, as a whole, under a large set of different physiological and pathological conditions. On the example of the reduced nicotinamide adenine dinucleotide (NADH)-ubiquinol-oxidoreductase (complex I) we analyze the suitability of different types of rate equations. Based on our kinetic experiments we show that very simple rate laws, as those often used in many respiratory chain models, fail to describe the kinetic behavior when applied to a wide concentration range. This led us to adapt rate equations containing the essential parameters of enzyme kinetic, maximal velocities and Henri-Michaelis-Menten like-constants (KM and KI) to satisfactorily simulate these data.
authors: Université de Bordeaux, Bordeaux, France; Institut für Biologie Theoretische Biophysik Humboldt-Universität zu Berlin, Invalidenstraße 42, Berlin, Germany; Laboratoire de métabolisme énergétique cellulaire, IBGC - CNRS UMR 5095, 1 Rue Camille Saint Saëns, 33077 Bordeaux, France.
authors: Margit
authors: M
authors: Heiske
authors: Institut de Mathématiques de Bordeaux, ENSTBB-Institut Polytechnique de Bordeaux, France.
authors: Christine
authors: C
authors: Nazaret
authors: Université de Bordeaux, Bordeaux, France; Laboratoire de métabolisme énergétique cellulaire, IBGC - CNRS UMR 5095, 1 Rue Camille Saint Saëns, 33077 Bordeaux, France. Electronic address: jpm@u-bordeaux2.fr.
authors: Jean-Pierre
authors: JP
authors: Mazat
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism*; D007700:Kinetics; D008962:Models, Theoretical; D009243:NAD / Q000378:metabolism
chemical_list: D009243:NAD; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I
keywords: Complex I; Modeling; Oxidative phosphorylation