vanBeek2007_OxPhos_HeartMuscleCells

  public model
Model Identifier
MODEL1006230027
Short description

This a model from the article:
Adenine nucleotide-creatine-phosphate module in myocardial metabolic system explains fast phase of dynamic regulation of oxidative phosphorylation.
van Beek JH. Am J Physiol Cell Physiol 2007 Sep;293(3):C815-29 17581855 ,
Abstract:
Computational models of a large metabolic system can be assembled from modules that represent a biological function emerging from interaction of a small subset of molecules. A "skeleton model" is tested here for a module that regulates the first phase of dynamic adaptation of oxidative phosphorylation (OxPhos) to demand in heart muscle cells. The model contains only diffusion, mitochondrial outer membrane (MOM) permeation, and two isoforms of creatine kinase (CK), in cytosol and mitochondrial intermembrane space (IMS), respectively. The communication with two neighboring modules occurs via stimulation of mitochondrial ATP production by ADP and P(i) from the IMS and via time-varying cytosolic ATP hydrolysis during contraction. Assuming normal cytosolic diffusion and high MOM permeability for ADP, the response time of OxPhos (t(mito); generalized time constant) to steps in cardiac pacing rate is predicted to be 2.4 s. In contrast, with low MOM permeability, t(mito) is predicted to be 15 s. An optimized MOM permeability of 21 mum/s gives t(mito) = 3.7 s, in agreement with experiments on rabbit heart with blocked glycolytic ATP synthesis. The model correctly predicts a lower t(mito) if CK activity is reduced by 98%. Among others, the following predictions result from the model analysis: 1) CK activity buffers large ADP oscillations; 2) ATP production is pulsatile in beating heart, although it adapts slowly to demand with "time constant" approximately 14 heartbeats; 3) if the muscle isoform of CK is overexpressed, OxPhos reacts slower to changing workload; and 4) if mitochondrial CK is overexpressed, OxPhos reacts faster.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: van Beek JH. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..

To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V4)
Related Publication
  • Adenine nucleotide-creatine-phosphate module in myocardial metabolic system explains fast phase of dynamic regulation of oxidative phosphorylation.
  • van Beek JH
  • American journal of physiology. Cell physiology , 9/ 2007 , Volume 293 , pages: C815-29 , PubMed ID: 17581855
  • Dept. of Molecular Cell Physiology, FALW, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam. hans.van.beek@falw.vu.nl
  • Computational models of a large metabolic system can be assembled from modules that represent a biological function emerging from interaction of a small subset of molecules. A "skeleton model" is tested here for a module that regulates the first phase of dynamic adaptation of oxidative phosphorylation (OxPhos) to demand in heart muscle cells. The model contains only diffusion, mitochondrial outer membrane (MOM) permeation, and two isoforms of creatine kinase (CK), in cytosol and mitochondrial intermembrane space (IMS), respectively. The communication with two neighboring modules occurs via stimulation of mitochondrial ATP production by ADP and P(i) from the IMS and via time-varying cytosolic ATP hydrolysis during contraction. Assuming normal cytosolic diffusion and high MOM permeability for ADP, the response time of OxPhos (t(mito); generalized time constant) to steps in cardiac pacing rate is predicted to be 2.4 s. In contrast, with low MOM permeability, t(mito) is predicted to be 15 s. An optimized MOM permeability of 21 mum/s gives t(mito) = 3.7 s, in agreement with experiments on rabbit heart with blocked glycolytic ATP synthesis. The model correctly predicts a lower t(mito) if CK activity is reduced by 98%. Among others, the following predictions result from the model analysis: 1) CK activity buffers large ADP oscillations; 2) ATP production is pulsatile in beating heart, although it adapts slowly to demand with "time constant" approximately 14 heartbeats; 3) if the muscle isoform of CK is overexpressed, OxPhos reacts slower to changing workload; and 4) if mitochondrial CK is overexpressed, OxPhos reacts faster.
Contributors
Camille Laibe

Metadata information

is
BioModels Database MODEL1006230027
isDescribedBy
PubMed 17581855
hasTaxon
Taxonomy Homo sapiens
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
occursIn
Brenda Tissue Ontology cardiac muscle
isVersionOf

Curation status
Non-curated


Original model(s)
http://models.cellml.org/exposure/0b04b5eca948f2f416b1871cd11b3130

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Model files

MODEL1006230027_url.xml SBML L2V4 representation of vanBeek2007_OxPhos_HeartMuscleCells 32.48 KB Preview | Download

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MODEL1006230027_urn.xml Auto-generated SBML file with URNs 36.03 KB Preview | Download
MODEL1006230027.m Auto-generated Octave file 10.83 KB Preview | Download
MODEL1006230027-biopax3.owl Auto-generated BioPAX (Level 3) 2.01 KB Preview | Download
MODEL1006230027.sci Auto-generated Scilab file 191.00 Bytes Preview | Download
MODEL1006230027.png Auto-generated Reaction graph (PNG) 5.04 KB Preview | Download
MODEL1006230027.xpp Auto-generated XPP file 8.81 KB Preview | Download
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MODEL1006230027-biopax2.owl Auto-generated BioPAX (Level 2) 1.06 KB Preview | Download
MODEL1006230027.pdf Auto-generated PDF file 173.12 KB Preview | Download

  • Model originally submitted by : Camille Laibe
  • Submitted: Jun 23, 2010 10:12:02 AM
  • Last Modified: Jun 25, 2010 1:35:21 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Jun 25, 2010 1:35:21 PM
    • Submitted by: Camille Laibe
    • With comment: Current version of vanBeek2007_OxPhos_HeartMuscleCells
  • Version: 1 public model Download this version
    • Submitted on: Jun 23, 2010 10:12:02 AM
    • Submitted by: Camille Laibe
    • With comment: Original import of vanBeek2007_OxPhos_HeartMuscleCells

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