Mouse Iron Distribution - Rich and Deficient iron diets (tracer)

Mouse Iron Distribution Dynamics
Dynamic model of iron distribution in mice. This model attempts to fit the radioiron tracer data from Lopes et al. 2010 for mice fed iron deficient and rich diets by adjusting the rate of iron intake (vDiet) and the hepcidin synthesis rate (vhepcidin) independently for each experiment. All other parameters are those that provide the best fit for the adequate diet.
This model includes the radioiron tracer species.
Differences in parameter values between deficient, rich, and adequate diets:
Diet | vDiet | vhepcidin |
Adequate | 0.00377422 | 1.7393e-08 |
Deficient | 0 | 8.54927e-09 |
Rich | 0.00415624 | 2.30942e-08 |
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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.
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari
Metadata information
is (3 statements)
BioModels Database MODEL1903040001
BioModels Database BIOMD0000000734
hasProperty (1 statement)
Connected external resources
Name | Description | Size | Actions |
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Model files |
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BIOMD0000000734.xml | SBML L2V4 representation of Parmar2017 - Mouse Iron Distribution - Deficient and rich iron diet (Tracer) | 197.05 KB | Preview | Download |
Additional files |
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Fig4_all.png | Figure 4 result images (reproduced) | 123.75 KB | Preview | Download |
Parmar2017_Deficient_Rich_tracer.cps | COPASI 4.24 (build196) file depicting literature figure 3 and 4. | 293.47 KB | Preview | Download |
Parmar2017_Deficient_Rich_tracer.sedml | SEDML file | 1.19 KB | Preview | Download |
- Model originally submitted by : Krishna Kumar Tiwari
- Submitted: Mar 4, 2019 4:40:13 PM
- Last Modified: Oct 10, 2019 4:16:43 PM
Revisions
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Version: 6
- Submitted on: Oct 10, 2019 4:16:43 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Automatically added model identifier BIOMD0000000734
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Version: 4
- Submitted on: Mar 4, 2019 4:40:13 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Automatically added model identifier BIOMD0000000734
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: Variable used inside SBML models
Species | Initial Concentration/Amount |
---|---|
FeDuo 0 iron cation |
0.0117590568706314 mol |
FeSpleen iron cation |
0.0 mol |
Fe2Tf Serotransferrin ; iron(3+) |
0.0 mol |
Fe2Tf 0 iron(3+) ; Serotransferrin |
1.35248196757048E-5 mol |
Tf Serotransferrin |
1.5821833083706E-5 mol |
Fe1Tf 0 Serotransferrin ; iron(3+) |
9.35334724058915E-6 mol |
Reactions | Rate | Parameters |
---|---|---|
Fe2Tf_0 => FeDuo_0 + Tf | kInDuo*Fe2Tf_0*Plasma | kInDuo = 0.0689984226081531 |
FeSpleen => NTBI; FeSpleen_0, Hepcidin | VSpleenNTBI*Spleen*FeSpleen/((Km+FeSpleen+FeSpleen_0)*(1+Hepcidin/Ki)) | VSpleenNTBI = 1.342204923; Km = 0.0159421218669513; Ki = 1.0E-9 |
FeBM_0 => FeSpleen | kBMSpleen*FeBM_0*BoneMarrow | kBMSpleen = 0.061902954378781 |
Fe2Tf => FeBM_0 + FeBM + Tf | kInBM*Fe2Tf*Plasma | kInBM = 15.7690636138556 |
Fe2Tf => FeRest + FeRest_0 + Tf | kInRest*Fe2Tf*Plasma | kInRest = 6.16356235352873 |
Fe1Tf_0 + NTBI_0 => Fe2Tf_0 | Plasma*kFe1Tf_Fe2Tf*Fe1Tf_0*NTBI_0 | kFe1Tf_Fe2Tf = 1.084322005E9 |
Fe1Tf + NTBI_0 => Fe2Tf | Plasma*kFe1Tf_Fe2Tf*Fe1Tf*NTBI_0 | kFe1Tf_Fe2Tf = 1.084322005E9 |
Fe2Tf_ => FeRest + Tf | kInRest*Fe2Tf_*Plasma | kInRest = 6.16356235352873 |
Fe1Tf + NTBI => Fe2Tf_ | Plasma*kFe1Tf_Fe2Tf*Fe1Tf*NTBI | kFe1Tf_Fe2Tf = 1.084322005E9 |
(added: 04 Mar 2019, 16:36:05, updated: 04 Mar 2019, 16:36:05)