Iron Biochemistry

Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows.

Our interest in iron biochemistry started with its role in breast cancer, through a collaboration with Suzy and Frank Torti and Reinhard Laubenbacher. Since then it has expanded to iron absorption and regulation and its role in other diseases (also in collaboration with Douglas Kell).

Iron metabolic network

Through an extensive literature review we delineated the metabolic network of iron in mammalian cells. This was then used as a template, together with gene expression data, for identifying the iron metabolism in several cell types: hepatocytes, reticulocytes, macrophages and intestinal cells. This network has been the template for our further models of iron biochemistry.

Iron regulation in the liver

A quantitative and dynamic model of liver iron metabolism was constructed that is able to reproduce physiological data from hemochromatosis patients. This model generated a number of hypotheses about iron regulation. This work is being extended to include iron absortion by the intestine, to form a more complete picture of iron regulation.

Dynamics of the core iron control network

A more theoretical work investigated the dynamic properties of the core metabolic network regulating iron and established that this is a stable dynamical system.