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creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
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creator:
  ORG:
    orgname: Max Delbrueck Center for Molecular Medicine
  n:
    given: Tiago Jose
    family: da Silva Lopes
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  W3 CDTF: Thu Aug 19 11:31:17 BST 2010
notes: This a model from the article: Systems analysis of iron metabolism: the network of iron pools and fluxes Tiago JS Lopes, Tatyana Luganskaja, Maja Vujic-Spasic, Matthias W Hentze, Martina U Muckenthaler, Klaus Schumann and Jens G Reich BMC Systems Biology 2010, Aug 13;4(1):112. 20704761 , Abstract: Background Every cell of the mammalian organism needs iron in numerous oxido-reductive processes as well as for transport and storage of oxygen. The 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 signaling 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…
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