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BIOMD0000000041 - Kongas2007 - Creatine Kinase in energy metabolic signaling in muscle

 

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Reference Publication
Publication ID: 10.1038/npre.2007.13...
Kongas O, van Beek JHGM
Creatine kinase in energy metabolic signaling in muscle
Nature Precedings 2007
Institute of Cybernetics, Tallinn Technical University, Estonia; VU University Amsterdam  [more]
Model
Original Model: BIOMD0000000041.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL6622188656
Submission Date: 13 Sep 2005 15:38:05 UTC
Last Modification Date: 10 Oct 2014 11:18:10 UTC
Creation Date: 29 Jun 2005 13:27:31 UTC
Encoders:  Nicolas Le Novère
   Maria Schilstra
   Rainer Machne
set #1
bqmodel:isDerivedFrom PubMed 10751324
set #2
bqbiol:hasTaxon Taxonomy Oryctolagus
bqbiol:isVersionOf Gene Ontology ATP metabolic process
Gene Ontology creatine metabolic process
Notes
Kongas2007 - Creatine Kinase in energy metabolic signaling in muscle

This model is described in the article:

Olav Kongas and Johannes H. G. M. van Beek
Available from Nature Precedings

Abstract:

There has been much debate on the mechanism of regulation of mitochondrial ATP synthesis to balance ATP consumption during changing cardiac workloads. A key role of creatine kinase (CK) isoenzymes in this regulation of oxidative phosphorylation and in intracellular energy transport had been proposed, but has in the mean time been disputed for many years. It was hypothesized that high-energy phosphorylgroups are obligatorily transferred via CK; this is termed the phosphocreatine shuttle. The other important role ascribed to the CK system is its ability to buffer ADP concentration in cytosol near sites of ATP hydrolysis.

Almost all of the experiments to determine the role of CK had been done in the steady state, but recently the dynamic response of oxidative phosphorylation to quick changes in cytosolic ATP hydrolysis has been assessed at various levels of inhibition of CK. Steady state models of CK function in energy transfer existed but were unable to explain the dynamic response with CK inhibited.

The aim of this study was to explain the mode of functioning of the CK system in heart, and in particular the role of different CK isoenzymes in the dynamic response to workload steps. For this purpose we used a mathematical model of cardiac muscle cell energy metabolism containing the kinetics of the key processes of energy production, consumption and transfer pathways. The model underscores that CK plays indeed a dual role in the cardiac cells. The buffering role of CK system is due to the activity of myofibrillar CK (MMCK) while the energy transfer role depends on the activity of mitochondrial CK (MiCK). We propose that this may lead to the differences in regulation mechanisms and energy transfer modes in species with relatively low MiCK activity such as rabbit in comparison with species with high MiCK activity such as rat.

The model needed modification to explain the new type of experimental data on the dynamic response of the mitochondria. We submit that building a Virtual Muscle Cell is not possible without continuous experimental tests to improve the model. In close interaction with experiments we are developing a model for muscle energy metabolism and transport mediated by the creatine kinase isoforms which now already can explain many different types of experiments.

The model has been designed according to the spirit of the paper. The list of rate in the appendix has been corrected as follow:

  1. d[ATP]/dt = (-Vhyd -Vmmck +Jatp) / Vcyt
  2. d[ADP]/dt = ( Vhyd +Vmmck +Jadp) / Vcyt
  3. d[PCr]/dt = ( Vmmck +Jpcr ) / Vcyt
  4. d[Cr]/dt = (-Vmmck +Jpcr ) / Vcyt
  5. d[Pi]/dt = ( Vhyd + Jpi ) / Vcyt
  6. d[ATPi]/dt = (+Vsyn -Vmick -Jatp) / Vims
  7. d[ADPi]/dt = (-Vsyn +Vmick -Jadp) / Vims
  8. d[PCri]/dt = ( Vmick -Jpcr ) / Vims
  9. d[Cri]/dt = (-Vmick -Jpcr ) / Vims
  10. d[Pii]/dt = (-Vsyn -Jpi ) / Vims

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 10.1038/npre.2007.13... Submission Date: 13 Sep 2005 15:38:05 UTC Last Modification Date: 10 Oct 2014 11:18:10 UTC Creation Date: 29 Jun 2005 13:27:31 UTC
Mathematical expressions
Reactions
Vsyn Vmick Vmmck Vhyd
Jpi Jcr Jadp Jpcr
Jatp      
Physical entities
Compartments Species
IMS ADPi ATPi Cri
PCri Pii  
CYT PCr ADP ATP
Cr Pi  
Reactions (9)
 
 Vsyn [ADPi] + [Pii] ↔ [ATPi];  
 
 Vmick [ATPi] + [Cri] ↔ [ADPi] + [PCri];  
 
 Vmmck [ATP] + [Cr] ↔ [PCr] + [ADP];  
 
 Vhyd [ATP] → [ADP] + [Pi];  
 
 Jpi [Pii] ↔ [Pi];  
 
 Jcr [Cri] ↔ [Cr];  
 
 Jadp [ADPi] ↔ [ADP];  
 
 Jpcr [PCri] ↔ [PCr];  
 
 Jatp [ATPi] ↔ [ATP];  
 
  Spatial dimensions: 3.0  Compartment size: 0.0625
 
 ADPi
Compartment: IMS
Initial concentration: 0.0
 
 ATPi
Compartment: IMS
Initial concentration: 0.0
 
 Cri
Compartment: IMS
Initial concentration: 0.0
 
 PCri
Compartment: IMS
Initial concentration: 0.0
 
 Pii
Compartment: IMS
Initial concentration: 32000.0
 
  Spatial dimensions: 3.0  Compartment size: 0.75
 
 PCr
Compartment: CYT
Initial concentration: 0.0
 
 ADP
Compartment: CYT
Initial concentration: 0.0
 
 ATP
Compartment: CYT
Initial concentration: 9700.0
 
 Cr
Compartment: CYT
Initial concentration: 26000.0
 
 Pi
Compartment: CYT
Initial concentration: 0.0
 
Vsyn (3)
 
   Vsynmax
Value: 4600.0
Constant
 
   Kadp
Value: 800.0
Constant
 
   Kpi
Value: 20.0
Constant
 
Vmick (8)
 
   Vf_2
Value: 2658.0
Constant
 
   Kia_2
Value: 750.0
Constant
 
   Kb_2
Value: 5200.0
Constant
 
   Vb_2
Value: 11160.0
Constant
 
   Kic_2
Value: 204.8
Constant
 
   Kd_2
Value: 500.0
Constant
 
   Kib_2
Value: 28800.0
Constant
 
   Kid_2
Value: 1600.0
Constant
 
Vmmck (8)
 
   Vf_3
Value: 6966.0
Constant
 
   Kia_3
Value: 900.0
Constant
 
   Kb_3
Value: 15500.0
Constant
 
   Vb_3
Value: 29250.0
Constant
 
   Kic_3
Value: 222.4
Constant
 
   Kd_3
Value: 1670.0
Constant
 
   Kib_3
Value: 34900.0
Constant
 
   Kid_3
Value: 4730.0
Constant
 
Vhyd (1)
 
   Vhyd
Value: 4600.0
Constant
 
Jpi (1)
 
   Rpi
Value: 18.4
Constant
 
Jcr (1)
 
   Rcr
Value: 14.6
Constant
 
Jadp (1)
 
   Radp
Value: 8.16
Constant
 
Jpcr (1)
 
   Jpcr
Value: 14.6
Constant
 
Jatp (1)
 
   Jatp
Value: 8.16
Constant
 
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