Introduction

In all mammalian cells, iron in excess of current metabolic requirements is incorporated into ferritin. Effective iron storage is an essential component of cellular iron homeostasis, because iron not sequestered within the cell can catalyze potentially cytotoxic free radical-generating reactions. Although all cells can store iron in ferritin, macrophages and hepatocytes are particularly adapted for this function and retain excess iron as a reserve for times of increased body iron needs. The hepatocyte can take up iron in a variety of different forms and act as a major site of available iron stores, and thus has a central ‘buffering’ role in internal iron exchange.

Because hemochromatosis is an iron storage disorder, ferritin, the principal iron storage protein, plays an important role in the disease. Ferritin sequesters the iron distributed throughout the body as a consequence of elevated intestinal iron absorption. The serum ferritin concentration accurately reflects the body iron load and provides a valuable diagnostic tool. The iron in ferritin is not biologically inert but can be utilized readily for various cellular functions. The ability of ferritin to release iron in times of demand is essential physiologically but also underlies the treatment of hemochromatosis by phlebotomy therapy.

Aspects of ferritin metabolism relevant to hemochromatosis will be discussed in this chapter. The areas covered include a brief overview of ferritin biochemistry, a discussion of ferritin synthesis and its regulation in the intestinal mucosa, the liver and the reticuloendothelial (RE) system, and the role played by the serum ferritin concentration in the diagnosis of hemochromatosis.