equivalent to a 10% increase in transferrin saturation as a simulation of oral iron dosage on hepatocytes. The simulated hepcidin response (Figure \[fig:IronResponse\]A) is consistent with the hepcidin response measured by Girelli [*et al.*]{} [@Girelli2011Time] (Figure \[fig:IronResponse\]B & C). The time scale and dynamics of the hepcidin response to iron challenge has been accurately replicated in the simulation presented here. Although the exact dynamics of the simulated response is not validated by either experimental technique (mass spectrometry or ELISA) the simulation appears to present an approximation of the two experimental techniques reaching a peak between 4 and 8 hours and returning to around basal levels within 24 hours.

Cellular Iron Regulation {#cellular-iron-regulation .unnumbered}
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The computational model supports the proposed role of HFE and TFR2 as sensors of systemic iron. Figure \[fig:IronChangeHFETfR\]B shows that as the concentration of HFE bound to TfR2 (HFE-TfR2) increases with serum transferrin-bound iron (Tf-Fe\_intercell), at the same time the abundance of HFE bound to TfR1 (HFE-TfR1) decreases. The increase in HFE-TfR2 complex, even though of small magnitude, promotes increased expression of hepcidin (Figure \[fig:IronChangeHFETfR\]A). It is through this mechanism that liver cells sense serum iron levels and control whole body iron metabolism through the action 