Iron is an essential element in living cells and part of many metabolic pathways including transport and storage of oxygen. Iron uptake mainly occurs in its ferrous form (Fe2+ ). Oxidized to ferric iron (Fe3+ ) it is bound to the transport protein transferrin and delivered to target tissues. After endocytosis iron is incorporated into cytochromes, oxygen-binding proteins or enzymes. Excess iron is stored in a protein complex as ferritin, mainly present in liver, spleen and bone marrow. The main amount of iron is found in hemoglobin. Aging erythrocytes undergo phagocytosis resulting in release of iron which binds to transferrin to re-enter the cycle.
Iron metabolism disorders are related to several significant diseases. Increased iron levels occur in hemochromatosis (iron overload) and liver damage, whereas decreased iron levels may cause anemia. Elevated transferrin levels can indicate iron deficiency, whereas the determination of transferrin saturation is used in screening for hemochromatosis to exclude iron overload in iron distribution disorders (e.g. in liver diseases). Variations of serum ferritin levels are closely related to changes in tissue ferritin. A decreased ferritin level indicates tissue iron depletion and is particularly useful in the early detection of iron deficiency anemia. Increased ferritin values may indicate iron overload in conjunction with hemochromatosis. Ferritin is also used for evaluation of chronic liver disease, infections, inflammation and malignancy. Normally, 1/3 of transferrin iron-binding sites are saturated by Fe3+. The reserve iron-binding capacity of transferrin is called the unsaturated iron-binding capacity (UIBC). The sum of UIBC and iron in serum represent the total iron-binding capacity (TIBC). Serum UIBC levels vary in disorders of iron metabolism where iron capacities are often increased in iron deficiency and decreased in chronic inflammatory disorders or malignancies.