Mechanism of Protection of Peroxidase Activity by Oscillatory Dynamics
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
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
reaction diagram
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.
O2
oxygen
O2_radical
oxygen free radical
O2_liquid
liquid oxygen
O2_gas
oxygen gas
NADH
nicotinamide adenine dinucleotide
NAD
oxidised nicotinamide adenine dinucleotide
NAD_radical
nicotinamide adenine dinucleotide free radical
NAD2
nicotinamide adenine dinucleotide
H2O2
peroxide
H
proton
Per3
ferric peroxidase
Per2
ferrous peroxidase
coI
compound I
coII
compound II
coIII
compound III
Ar_radical
aromatic compound free radical
ArH
aromatic compound
2003-07
Catherine Lloyd
Ursula
Kummer
Catherine
Lloyd
May
keyword
peroxidase
oscillator
metabolism
c.lloyd@auckland.ac.nz
2004-01-22
The University of Auckland, Auckland Bioengineering Institute
Olsen et al.'s 2003 mathematical model of the peroxidase-oxidase reaction.
European Journal of Biochemistry
Lars
Olsen
F
The University of Auckland
Auckland Bioengineering Institute
12823550
Marcus
Hauser
B
J
This is the CellML description of Olsen et al.'s 2003 mathematical model of the peroxidase-oxidase reaction.
Mechanism of protection of peroxidase activity by oscillatory dynamics
270
2796
2804