A general map of iron metabolism and tissue-specific subnetworks

Abstract

Iron is required for survival of mammalian cells. Recently, understanding of iron metabolism and trafficking has increased dramatically, revealing a complex, interacting network largely unknown just a few years ago. This provides an excellent model for systems biology development and analysis. The first step in such an analysis is the construction of a structural network of iron metabolism, which we present here. This network was created using CellDesigner version 3.5.2 and includes reactions occurring in mammalian cells of numerous tissue types. The iron metabolic network contains 151 chemical species and 107 reactions and transport steps. Starting from this general model, we construct iron networks for specific tissues and cells that are fundamental to maintaining body iron homeostasis. We include subnetworks for cells of the intestine and liver, tissues important in iron uptake and storage, respectively; as well as the reticulocyte and macrophage, key cells in iron utilization and recycling. The addition of kinetic information to our structural network will permit the simulation of iron metabolism in different tissues as well as in health and disease.

Iron Regulatory Proteins: From Molecular Mechanisms to Drug Development

“…As approximately 70% of body iron is found in hemoglobin, most of the circulating iron is consumed for heme biosynthesis by immature bone marrow erythrocytes, which internalize Tf through the transferrin receptor (TfR1) (Fig. 2) (81). The liver stores 10%-20% of body iron in the form of ferritin, which can be easily mobilized when needed.…”

Insect transferrins: Multifunctional proteins

“…Iron is an extremely attractive prosthetic biocatalyst or electron carrier because it can readily change oxidation and coordination states. Despite its requirement and these valuable features, excessive or misplaced iron is highly destructive because it can generate oxygen radicals by the Fenton-Haber Weiss reaction [5,6]. Iron-catalyzed oxidative stress can have many adverse consequences [7].…”

Coronary Artery Disease and Oxidative Stress

“…A study from our laboratory compared patients with coronary heart disease and sleep apnea (also inflammation disease) showing that serum ferritin levels increased in coronary heart disease patients and positively correlated with sleep apnea. These studies are supported by the evidences that show iron deposition in human atherosclerotic lesions, suggesting that iron may play a role in the development of atherosclerosis (Hower et al, 2009). …”