A model of oxidative phosphorylation in mammalian skeletal muscle
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This model is valid CellML but it will not run in OpenCell or COR and it requires much more curation.
Model Structure
ABSTRACT: A dynamic computer model of oxidative phosphorylation in oxidative mammalian skeletal muscle was developed. The previously published model of oxidative phosphorylation in isolated skeletal muscle mitochondria was extended by incorporation of the creatine kinase system (creatine kinase plus phosphocreatine/creatine pair), cytosolic proton production/consumption system (proton production/consumption by the creatine kinase-catalysed reaction, efflux/influx of protons), physiological size of the adenine nucleotide pool and some additional minor changes. Theoretical studies performed by means of the extended model demonstrated that the CK system, which allows for large changes in P(i) in relation to isolated mitochondria system, has no significant influence on the kinetic properties of oxidative phosphorylation, as inorganic phosphate only slightly modifies the relationship between the respiration rate and [ADP]. Computer simulations also suggested that the second-order dependence of oxidative phosphorylation on [ADP] proposed in the literature refers only to the ATP synthesis flux, but not to the oxygen consumption flux (the difference between these two fluxes being due to the proton leak). Next, time courses of changes in fluxes and metabolite concentrations during transition between different steady-states were simulated. The model suggests, in accordance with previous theoretical predictions, that activation of oxidative phosphorylation by an increase in [ADP] can (roughly) explain the behaviour of the system only at low work intensities, while at higher work intensities parallel activation of different steps of oxidative phosphorylation is involved.
The original paper reference is cited below:
A model of oxidative phosphorylation in mammalian skeletal muscle, Bernard Korzeniewski and Jerzy A. Zoladz, 2001, Biophysical Chemistry, 92, 17-34. PubMed ID: 11527576
the conventional rendering of oxidative phosphorylation
A schematic diagram of the oxidative phosphorylation pathway.
external monovalent inorganic phosphate
Pi_je
keyword
mammalian
skeletal muscle
myocyte
metabolism
oxidative phosphorylation
The University of Auckland, Auckland Bioengineering Institute
reduced ubiquinone
UQH2
oxidised nicotinamide adenine dinucleotide
NAD
2001-08-30
internal monovalent inorganic phosphate
Pi_ji
The University of Auckland
Auckland Bioengineering Institute
Bernard
Korzeniewski
creatine
Cr
11527576
This is the CellML description of Korzeniewski and Froncisz's
mathematical model of oxidative phosphorylation (1991). In 1996 they
further modified and developed the model, making it specific to liver
hepatocytes. Most recent changes (2001) have extended the model and
have made it specific to mammalian skeletal muscle. These changes
have been incorporated into the CellML description.
The model distinguishes three modes of the work of cells. The rate
equations for some reactions are slightly altered, dependent on the
mode of work. This CellML description concentrates on mode 1 only,
where;
1) Beta-oxidation of fatty acids as the source of reducing
equivalents, fatty acids as a respiratory substrate, no additional ATP
supply (glycolysis), only "basal" ATP consumption (protein synthesis,
ion transport).
phosphocreatine
PCr
free external adenosine triphosphate
ATP_fe
Catherine Lloyd
free internal adenosine triphosphate
ATP_fi
oxidised cytochrome C
c_3
Catherine
Lloyd
May
2007-05-31T00:00:00+00:00
A model of oxidative phosphorylation in mammaliam skeletal muscle
92
17
34
external magnesium-complexed adenosine triphosphate
ATP_me
reduced nicotinamide adenine dinucleotide
NADH
2008-09-02T14:26:09+12:00
James
Lawson
Richard
reduced cytochrome a3
a_2
oxidised cytochrome a3
a_3
Fixed error mentioned in https://tracker.physiomeproject.org/show_bug.cgi?id=219
Model still has invalid connection to be fixed.
2007-06-05T09:48:29+12:00
The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics. This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
The model does not run in the PCEnv simulator because the model is overconstrained. But I can't work out which equation(s) or initial value(s) to remove. I suspect PCEnv is calculating the value of "u" itself from early equations.
internal magnesium-complexed adenosine triphosphate
ATP_mi
Catherine
Lloyd
May
oxygen
O2
free internal magnesium
Mg_fi
total internal inorganic phosphate
Pi_ti
free external adenosine diphosphate
ADP_fe
oxidised ubiquinone
UQ
free internal adenosine diphosphate
ADP_fi
2008-09-02T14:12:01+12:00
A dynamic model of oxidative phosphorylation
Skeletal Myocyte
Mammalia
free external magnesium
Mg_fe
total external inorganic phosphate
Pi_te
total internal adenosine triphosphate
ATP_ti
reduced cytochrome C
c_2
c.lloyd@auckland.ac.nz
James
Lawson
Richard
Deleted an extraneous connection element randomly sitting within a component element. Model still overconstrained.
Biophysical Chemistry
total external adenosine triphosphate
ATP_te
external magnesium-complexed adenosine diphosphate
ADP_me
total internal adenosine diphosphate
ADP_ti
Jerzy
Zoladz
A
total phosphate pool
P_SUM
internal protons
Hi
free external adenosine monophosphate
AMP_fe
external protons
He
internal magnesium-complexed adenosine diphosphate
ADP_mi
total external adenosine diphosphate
ADP_te