This model is according to the paper from Axel Kowald Alternative pathways as mechanism for the negative effects associated with overexpression of superoxide dismutase.
Reactions from 1 to 17 are listed in the paper, note that for clarity species whose concentrations are assumed to be constant (e.g.water, oxygen,protons, metal ions) are omitted from the diagram. In the paper, v16 is a fast reaction, but we do not use fast reaction in the model.
Figure2 has been reproduced by both SBMLodeSolver and Copasi4.0.20(development) . Figure 3 has been obtained with Copasi4.0.20(development) using parameter scan.
The steady-state of [LOO*] a little bit lower than showed on the paper, I guess it may be the simulation method used in the paper use fast reaction and also the reaction (5) listed on Page 831 on the paper is slightly different from equation (2) on Page 832. The rest of them are the quite the same.
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- Alternative pathways as mechanism for the negative effects associated with overexpression of superoxide dismutase.
- Kowald A, Lehrach H, Klipp E
- Journal of theoretical biology , 2/ 2006 , Volume 238 , pages: 828-840
- Kinetic Modelling Group, Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany. email@example.com
- One of the most important antioxidant enzymes is superoxide dismutase (SOD), which catalyses the dismutation of superoxide radicals to hydrogen peroxide. The enzyme plays an important role in diseases like trisomy 21 and also in theories of the mechanisms of aging. But instead of being beneficial, intensified oxidative stress is associated with the increased expression of SOD and also studies on bacteria and transgenic animals show that high levels of SOD actually lead to increased lipid peroxidation and hypersensitivity to oxidative stress. Using mathematical models we investigate the question how overexpression of SOD can lead to increased oxidative stress, although it is an antioxidant enzyme. We consider the following possibilities that have been proposed in the literature: (i) Reaction of H(2)O(2) with CuZnSOD leading to hydroxyl radical formation. (ii) Superoxide radicals might reduce membrane damage by acting as radical chain breaker. (iii) While detoxifying superoxide radicals SOD cycles between a reduced and oxidized state. At low superoxide levels the intermediates might interact with other redox partners and increase the superoxide reductase (SOR) activity of SOD. This short-circuiting of the SOD cycle could lead to an increased hydrogen peroxide production. We find that only one of the proposed mechanisms is under certain circumstances able to explain the increased oxidative stress caused by SOD. But furthermore we identified an additional mechanism that is of more general nature and might be a common basis for the experimental findings. We call it the alternative pathway mechanism.
- Model originally submitted by : Enuo He
- Submitted: Apr 9, 2007 8:30:35 PM
- Last Modified: Oct 9, 2014 4:46:31 PM
(added: 29 Mar 2007, 01:45:06, updated: 29 Mar 2007, 01:45:06)