Helmholtz Gemeinschaft


Systems analysis of iron metabolism: the network of iron pools and fluxes

[thumbnail of 11156oa.pdf] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Item Type:Article
Title:Systems analysis of iron metabolism: the network of iron pools and fluxes
Creators Name:Lopes, T.J., Luganskaja, T., Vujic-Spasic, M., Hentze, M.W., Muckenthaler, M.U., Schumann, K. and Reich, J.G.
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 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.
Keywords:Biological Transport, Biomechanics, Computational Biology, Erythropoiesis, Homeostasis, Iron, Metabolic Clearance Rate, Biological Models, Time Factors, Animals, Mice
Source:BMC Systems Biology
Publisher:BioMed Central
Page Range:112
Date:13 August 2010
Official Publication:https://doi.org/10.1186/1752-0509-4-112
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library