Olsen, Hauser, Kummer, 2003

Model Status

This model runs in COR and OpenCell and the units are consistent throughout. At present it does not reproduce the published results, although the equations are a faithful match to the paper. Oscillatory behavior is seen in the published figures but cannot be reproduced in CellML, and is probably a result of an additional equation describing oxygen fluctuations. However, when run to steady state the state variables are close to published steady state values.

Model Structure

ABSTRACT: The peroxidase-oxidase reaction is known to involve reactive oxygen species as intermediates. These intermediates inactivate many types of biomolecules, including peroxidase itself. Previously, we have shown that oscillatory dynamics in the peroxidase-oxidase reaction seem to protect the enzyme from inactivation. It was suggested that this is due to a lower average concentration of reactive oxygen species in the oscillatory state compared to the steady state. Here, we studied the peroxidase-oxidase reaction with either 4-hydroxybenzoic acid or melatonin as cofactors. We show that the protective effect of oscillatory dynamics is present in both cases. We also found that the enzyme degradation depends on the concentration of the cofactor and on the pH of the reaction mixture. We simulated the oscillatory behaviour, including the oscillation/steady state bistability observed experimentally, using a detailed reaction scheme. The computational results confirm the hypothesis that protection is due to lower average concentrations of superoxide radical during oscillations. They also show that the shape of the oscillations changes with increasing cofactor concentration resulting in a further decrease in the average concentration of radicals. We therefore hypothesize that the protective effect of oscillatory dynamics is a general effect in this system.

The original paper reference is cited below:

Mechanism of protection of peroxidase activity by oscillatory dynamics, Lars F. Olsen, Marcus J. B. Hauser and Ursula Kummer, 2003, European Journal of Biochemistry, 270, 2796-2804. PubMed ID: 12823550

Schematic diagram of the peroxidase-oxidase reaction. Per3+ and Per2+ indicate iron(III) and iron(II) peroxidase respectively. Enzyme intermediates compound I, II and III are represented as coI, coII, and coIII. ArH and Ar' indicate the aromatic compound 4-hydroxybenzoic acid, or melatonin, and its free radical respectively.
Derived from workspace Olsen, Hauser, Kummer, 2003 at changeset d6c238f05a03.
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