Olsen, Hauser, Kummer, 2003

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

In spite of their wide spread occurance, the functions of metabolic oscillations in cells are not well understood. They may be a side-effect of the nonlinear properties of metabolic enzymes, or they may actually serve an important fuction in their own right. Over the years several potential roles for metabolic oscillations have been suggested, such increasing the thermodynamic efficiency of metabolism, encoding transmembrane signalling, acting as a biological clock, and protecting proteins against substances such as reactive oxygen species, or radicals, that are synthesised as a by product of cell metabolism or signalling.

The peroxidase-oxidase reaction is one such reaction which is known to have reactive oxygen species as intermediates. These intermediates are able to inactivate many types of biomolecules, including the peroxidase enzyme itself. Oscillatory dynamics seem to protect the enzyme from this inactivation, may be because the average concentration of the oscillating reactive oxygen species is lower than its steady state concentration.

In the Olsen et al. 2003 publication described here, the authors study the peroxidase-oxidase reaction with either 4-hydroxybenzoic acid or melatonin as cofactors. In both cases, the oscillatory dynamics of the reactive oxygen species had a protective effect. They then went onto to simulate these experimental results with a mathematical model (see the figure below). The simulation results support the hypothesis that enzyme protection is due to the lower average concentration of the reactive oxygen species during oscillations. In addition, increasing the cofactor concentrations further decreased the avaerage concentration of the radicals.

The complete 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. (Full text (HTML) and PDF versions of the article are available on the European Journal of Biochemistry website.) 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.