2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016
1 - University of Castilla-La Mancha, Spain
Keywords: Hydrogen peroxide, Hemoproteins, Oxidative stress, COPASI, simulation
Catalase-like activity of hemoproteins has a great physiological importance because it contributes to eliminate the excess of hydrogen peroxide, an oxygen reactive species whose high concentration in biological organisms can be very dangerous. Hydrogen peroxide triggers redox cycles with these proteins, leading to protein inactivation and oxygen evolution. In the present work, the catalase-like oxygen production by a hemoprotein in the presence of hydrogen peroxide was kinetically characterized with a Clark-type electrode. By considering all the experimental data obtained, a possible mechanism was proposed, including: (a) competition between the one-electron and the two-electron reductions of the oxoferryl free radical species of the hemoprotein, giving rise to the ferryl state and the met state of the protein, respectively; (b) competition between the superoxide-dependent inactivation of the protein and its reduction back to the met state. Computer simulations of the model were performed by numerically integrating the differential equations set describing the mechanism using COPASI 4.7 software, which was seen to yield predictions of the kinetic parameters variation consistently with the kinetic behavior experimentally observed. The apparent inactivation constants and partition ratio calculated were in agreement with the theoretical results obtained by computer simulation. We suggest that the catalase-like activity of hemoproteins must predominantly be a biocatalytic reaction that protects the protein against hydrogen peroxide induced suicide inactivation. Among the enzymes and proteins that could follow this mechanism are peroxidases, catalases and cytochrome c, which are very important in the defense of the biological organisms against the oxidative stress.