Mouse Iron Distribution - Deficient iron diet (No Tracer)

Model Identifier
BIOMD0000000737
Short description
Mouse Iron Distribution Dynamics
Dynamic model of iron distribution in mice. This model includes only normal iron with the parameters that fit the data from Lopes et al. 2010 for mice fed a deficient iron diet.
This model does not include the radioiron tracer species. It is appropriate to study the properties in conditions where no tracers are used (for example for steady state analysis).
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
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Pedro Mendes, Krishna Kumar Tiwari
Metadata information
hasTaxon (1 statement)
is (3 statements)
hasProperty (1 statement)
is (3 statements)
Gene Ontology
iron ion homeostasis
BioModels Database MODEL1605030004
BioModels Database BIOMD0000000737
BioModels Database MODEL1605030004
BioModels Database BIOMD0000000737
hasProperty (1 statement)
Curation status
Curated
Modelling approach(es)
Tags
Connected external resources
Name | Description | Size | Actions |
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Model files |
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Parmar2017_Deficient_NoTracer.xml | SBML L2V4 representation of Parmar2017 - Mouse Iron Distribution - Deficient iron diet (No Tracer) | 108.40 KB | Preview | Download |
Additional files |
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MODEL1605030004-biopax2.owl | Auto-generated BioPAX (Level 2) | 31.11 KB | Preview | Download |
MODEL1605030004-biopax3.owl | Auto-generated BioPAX (Level 3) | 52.00 KB | Preview | Download |
MODEL1605030004.m | Auto-generated Octave file | 13.62 KB | Preview | Download |
MODEL1605030004.png | Auto-generated Reaction graph (PNG) | 150.31 KB | Preview | Download |
MODEL1605030004.sci | Auto-generated Scilab file | 5.99 KB | Preview | Download |
MODEL1605030004.svg | Auto-generated Reaction graph (SVG) | 45.84 KB | Preview | Download |
MODEL1605030004.vcml | Auto-generated VCML file | 897.00 Bytes | Preview | Download |
MODEL1605030004.xpp | Auto-generated XPP file | 9.94 KB | Preview | Download |
MODEL1605030004_urn.xml | Auto-generated SBML file with URNs | 98.05 KB | Preview | Download |
Parmar2017_Deficient_NoTracer.cps | COPASI 4.24 (build196) file depicting Deficient Table 3 results | 163.66 KB | Preview | Download |
Parmar2017_Deficient_NoTracer.sedml | SEDML file | 13.79 KB | Preview | Download |
- Model originally submitted by : Pedro Mendes
- Submitted: May 3, 2016 8:49:32 PM
- Last Modified: Mar 4, 2019 4:45:48 PM
Revisions
-
Version: 5
- Submitted on: Mar 4, 2019 4:45:48 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Automatically added model identifier BIOMD0000000737
-
Version: 2
- Submitted on: May 19, 2017 4:27:59 PM
- Submitted by: Pedro Mendes
- With comment: Current version of Parmar2017 - Mouse Iron Distribution - Deficient iron diet
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Version: 1
- Submitted on: May 3, 2016 8:49:32 PM
- Submitted by: Pedro Mendes
- With comment: Original import of Mouse Iron Distribution - Deficient iron diet
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Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
Species | Initial Concentration/Amount |
---|---|
FeRBC iron cation |
0.0379799887571665 mol |
Tf Serotransferrin |
1.5821833083706E-5 mol |
FeDuo iron cation |
0.0117590568706314 mol |
Hepcidin Hepcidin |
2.30017456622937E-8 mol |
Fe2Tf Serotransferrin ; iron(3+) |
1.35248196757048E-5 mol |
FeBM iron cation |
0.00303783614844319 mol |
FeLiver iron cation |
0.00200010981212238 mol |
NTBI iron cation |
3.3311210465159E-8 mol |
Reactions
Reactions | Rate | Parameters |
---|---|---|
FeBM => FeRBC | kInRBC*FeBM*BoneMarrow | kInRBC = 1.08447580176706 |
Fe2Tf => FeBM + Tf | kInBM*Fe2Tf*Plasma | kInBM = 15.7690636138556 |
Fe2Tf => FeDuo + Tf | kInDuo*Fe2Tf*Plasma | kInDuo = 0.0689984226081531 |
Hepcidin => | Plasma*k1*Hepcidin | k1=0.75616 |
Fe2Tf => FeLiver + Tf | kInLiver*Fe2Tf*Plasma | kInLiver = 2.97790545667672 |
Fe1Tf => FeLiver + Tf | kInLiver*Fe1Tf*Plasma | kInLiver = 2.97790545667672 |
=> Hepcidin | Plasma*v | v=8.54927E-9 |
FeSpleen => NTBI; Hepcidin | VSpleenNTBI*Spleen*FeSpleen/((Km+FeSpleen)*(1+Hepcidin/Ki)) | VSpleenNTBI = 1.342204923; Km = 0.0159421218669513; Ki = 1.0E-9 |
Curator's comment:
(added: 04 Mar 2019, 16:19:04, updated: 04 Mar 2019, 16:19:04)
(added: 04 Mar 2019, 16:19:04, updated: 04 Mar 2019, 16:19:04)
Reproduced Figure: Reproduced the reported data of total iron mass reduce by 23 % (2.2 to 1.7 mg) and transferrin saturation from 47 to 37%.
Simulation condition: Time for simulation: 100 days. Value of vDiet changed according to Deficient diet condition.
Mode is reproduced and simulated using COPASI 4.24 (build 196). Figures are created using libreoffice calc.