the regulation of iron. Recently, an increasing amount of detail has been discovered about molecules related to iron metabolism, but an understanding of how they work together and regulate iron levels (in healthy people) or fail to do it (in disease) is still missing. We present a mathematical model of the regulation of liver iron metabolism that provides explanations of its dynamics and allows further hypotheses to be formulated and later tested in experiments. Importantly, the model reproduces accurately the healthy liver iron homeostasis and simulates haemochromatosis showing how the causative mutation leads to iron overload. We investigate how best to control iron regulation and identified reactions that can be targets of new medicines to treat iron overload. The model provides a virtual laboratory for investigating iron metabolism and improves understanding of the method by which the liver senses and controls iron levels.

Introduction {#introduction .unnumbered}
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Iron is an essential element from archaea to complex eukaryotes and man [@Aisen2001Chemistry], and is required for many processes including oxygen transport, DNA synthesis and respiration. Iron deficiency is the most common nutritional deficiency affecting a large proportion of all humans [@TussingHumphreys2012Review]. The redox activity which provides iron’s utility also means poorly regulated 