Mouse Iron Distribution - Adequate iron diet (tracer)

  public model
Model Identifier
BIOMD0000000735
Short description

Mouse Iron Distribution Dynamics

Dynamic model of iron distribution in mice. This model includes normal iron and radioactive labelled tracer iron species and was used for parameter estimation given the data from Lopes et al. 2010 for mice fed an adequate iron diet.

Format
SBML (L2V4)
Related Publication
  • Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient.
  • Parmar JH, Davis G, Shevchuk H, Mendes P
  • BMC systems biology , 5/ 2017 , Volume 11 , Issue 1 , pages: 57 , PubMed ID: 28521769
  • Center for Quantitative Medicine and Department of Cell Biology, UConn Health, Farmington, CT, 06030, USA.
  • Iron is an essential element of most living organisms but is a dangerous substance when poorly liganded in solution. The hormone hepcidin regulates the export of iron from tissues to the plasma contributing to iron homeostasis and also restricting its availability to infectious agents. Disruption of iron regulation in mammals leads to disorders such as anemia and hemochromatosis, and contributes to the etiology of several other diseases such as cancer and neurodegenerative diseases. Here we test the hypothesis that hepcidin alone is able to regulate iron distribution in different dietary regimes in the mouse using a computational model of iron distribution calibrated with radioiron tracer data.A model was developed and calibrated to the data from adequate iron diet, which was able to simulate the iron distribution under a low iron diet. However simulation of high iron diet shows considerable deviations from the experimental data. Namely the model predicts more iron in red blood cells and less iron in the liver than what was observed in experiments.These results suggest that hepcidin alone is not sufficient to regulate iron homeostasis in high iron conditions and that other factors are important. The model was able to simulate anemia when hepcidin was increased but was unable to simulate hemochromatosis when hepcidin was suppressed, suggesting that in high iron conditions additional regulatory interactions are important.
Contributors
Submitter of the first revision: Pedro Mendes
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Pedro Mendes, Krishna Kumar Tiwari

Metadata information

isDescribedBy (1 statement)
PubMed 28521769

hasTaxon (1 statement)
Taxonomy Mus musculus

is (3 statements)
Gene Ontology iron ion homeostasis
BioModels Database MODEL1605030002
BioModels Database BIOMD0000000735

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
Parmar2017_Adequate_tracer.xml SBML L2V4 representation of Parmar2017 - Mouse Iron Distribution - Adequate iron diet (tracer) 195.21 KB Preview | Download

Additional files
MODEL1605030002-biopax2.owl Auto-generated BioPAX (Level 2) 65.83 KB Preview | Download
MODEL1605030002-biopax3.owl Auto-generated BioPAX (Level 3) 115.00 KB Preview | Download
MODEL1605030002.m Auto-generated Octave file 24.48 KB Preview | Download
MODEL1605030002.png Auto-generated Reaction graph (PNG) 683.78 KB Preview | Download
MODEL1605030002.sci Auto-generated Scilab file 67.00 Bytes Preview | Download
MODEL1605030002.svg Auto-generated Reaction graph (SVG) 107.19 KB Preview | Download
MODEL1605030002.vcml Auto-generated VCML file 897.00 Bytes Preview | Download
MODEL1605030002.xpp Auto-generated XPP file 17.63 KB Preview | Download
MODEL1605030002_urn.xml Auto-generated SBML file with URNs 177.90 KB Preview | Download
Parmar2017_Adequate_tracer.cps COPASI 4.24 (build196) file depicting literature figure 2 261.65 KB Preview | Download
Parmar2017_Adequate_tracer.sedml SEDML file 1.15 KB Preview | Download

  • Model originally submitted by : Pedro Mendes
  • Submitted: May 3, 2016 8:41:26 PM
  • Last Modified: Mar 4, 2019 4:44:47 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Mar 4, 2019 4:44:47 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000735
  • Version: 2 public model Download this version
    • Submitted on: May 19, 2017 4:23:10 PM
    • Submitted by: Pedro Mendes
    • With comment: Current version of Parmar2017 - Mouse Iron Distribution - Adequate iron diet (tracer)
  • Version: 1 public model Download this version
    • Submitted on: May 3, 2016 8:41:26 PM
    • Submitted by: Pedro Mendes
    • With comment: Original import of Mouse Iron Distribution - Adequate iron diet (tracer)

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Tf

Serotransferrin 		1.5821833083706E-5 mol
FeRest

iron cation 		0.0 mol
FeRest 0

iron cation 		2.86841656341217E-4 mol
NTBI

iron cation 		0.0 mol
Fe2Tf

iron(3+) ; Serotransferrin 		0.0 mol
FeDuo

iron cation 		0.0 mol
Reactions
Reactions Rate Parameters
Fe2Tf_ => FeRest + Tf kInRest*Fe2Tf_*Plasma kInRest = 6.16356235352873
Fe1Tf_0 => FeDuo_0 + Tf kInDuo*Fe1Tf_0*Plasma kInDuo = 0.0689984226081531
FeRest => NTBI; FeRest_0, Hepcidin VRestNTBI*RestOfBody*FeRest/((Km+FeRest+FeRest_0)*(1+Hepcidin/Ki)) VRestNTBI = 0.0109451335200198; Km = 0.0159421218669513; Ki = 1.0E-9
Fe1Tf => FeRest + Tf kInRest*Fe1Tf*Plasma kInRest = 6.16356235352873
Fe2Tf => FeRest + FeRest_0 + Tf kInRest*Fe2Tf*Plasma kInRest = 6.16356235352873
FeDuo => NTBI; FeDuo_0, Hepcidin VDuoNTBI*Duodenum*FeDuo/((Km+FeDuo+FeDuo_0)*(1+Hepcidin/Ki)) Km = 0.0159421218669513; VDuoNTBI = 0.200241893786814; Ki = 1.0E-9
FeLiver => NTBI; FeLiver_0, Hepcidin VLiverNTBI*Liver*FeLiver/((Km+FeLiver+FeLiver_0)*(1+Hepcidin/Ki)) VLiverNTBI = 0.0261147638001175; Km = 0.0159421218669513; Ki = 1.0E-9
Fe2Tf_ => FeLiver + Tf kInLiver*Fe2Tf_*Plasma kInLiver = 2.97790545667672
Fe1Tf + NTBI => Fe2Tf_ Plasma*kFe1Tf_Fe2Tf*Fe1Tf*NTBI kFe1Tf_Fe2Tf = 1.084322005E9
Fe1Tf => FeDuo + Tf kInDuo*Fe1Tf*Plasma kInDuo = 0.0689984226081531
Curator's comment:
(added: 04 Mar 2019, 15:58:06, updated: 04 Mar 2019, 15:58:06)
Reproduced Figure: Figure 2 of Literature. Simulation Condition: Simulation in COPASI need to be done as Tasks --> parameter Estimation --> Run (Method: Current Solution Statistics). Mode is reproduced and simulated in COPASI 4.24 (build 196) and figures are generated using Libreoffice calc.