re1
s1 > s2
re10
s1 > s7
re11
s1 > s9
re12
s1 > s8
re14
s9 > s10
re15
s8 > s10
re16
s1 > s11
re17
s11 > s1
re18
s1 > s12
re19
s12 > s1
re2
s2 > s3
re22
s1 > s13
re23
s13 > s1
re24
s1 > s14
re25
s14 > s1
re26
s1 > s15
re28
s1 > s16
re29
s16 > s1
re3
s3 > s4
re30
s1 > s17
re31
s17 > s1
re32
s7 > s1
re33
s15 > s10
re4
s4 > s1
re5
s2 > s4
re6
s1 > s5
re7
s5 > s1
re8
s1 > s6
re9
s6 > s1
Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.
Systems analysis of iron metabolism: the network of iron pools and fluxes.
BMC Syst Biol 2010;
4
:
112
- PubMed: 20704761
- PubMed Central: PMC2942822
- DOI: 10.1186/1752-0509-4-112
- ISSN: 1752-0509
- URL: https://ncbi.nlm.nih.gov/pubmed/20704761
Abstract
BACKGROUND: Every cell of the mammalian organism needs iron as trace element in numerous oxido-reductive processes as well as for transport and storage of oxygen. The very versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in the cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, excretion and intra-body distribution. Intracellular regulation in different cell types is intertwined with a global hormonal signalling structure. Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole.
RESULTS: Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on ferrokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, iron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartment) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearance rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distribution into different organs, of tracer-accessible pool sizes and of residence times of iron in the different compartments in response to three states of iron-repletion induced by the dietary regime.
CONCLUSIONS: This mathematical model presents a comprehensive physiological picture of mice under three different diets with varying iron contents. The quantitative results reflect systemic properties of iron metabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron storage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place.
RESULTS: Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on ferrokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, iron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartment) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearance rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distribution into different organs, of tracer-accessible pool sizes and of residence times of iron in the different compartments in response to three states of iron-repletion induced by the dietary regime.
CONCLUSIONS: This mathematical model presents a comprehensive physiological picture of mice under three different diets with varying iron contents. The quantitative results reflect systemic properties of iron metabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron storage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000261)
Biomodels notes: This model corresponds to the Iron Loaded model of the reference publication. The model reproduces the plots in third column (Diet: Iron Loaded) of figures 2 and 3. The model was integrated and simulated using Copasi v4.5.31.
JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.