Iron and Transferrin Metabolism

Study Notes

Iron absorption is a process occurring in the duodenum and proximal jejunum
Iron must be in the ferrous state (Fe2+) or bound to a protein like haem to be absorbed
The acidic environment in the proximal duodenum allows the enzyme cytochrome B (Dcytb) to convert insoluble Fe3+ to absorbable Fe2+
Iron is absorbed by the enterocyte via DMT1, stored as ferritin, or exported into the plasma by ferroportin
Upon exit, Fe2+ is oxidised by hephaestin or ceruloplasmin, binding to apotransferrin to form holotransferrin
Holotransferrin is internalised by target cells, and Fe3+ dissociates and is reduced by STEAP3
Fe2+ is incorporated into protoporphyrin IX by ferrochelatase

Apotransferrin (iron-free transferrin) is in the plasma, and binds Fe3+ to form holotransferrin
Holotransferrin delivers iron to cells
Transferrin receptors on cell membranes bind onto holotransferrin
H+ ions lead to iron release into the cell via a H+ ATPase
Iron is then incorporated into protoporphyrin

Serum Iron: Measures Fe3+ bound to transferrin, not a valuable measurement by itself. Free iron is not measured and so doesn't indicate bioavailability. Subject to daily variation but is often low in iron deficiency. Used for calculating Transferrin Saturation.
Transferrin Saturation (TSAT): The ratio of serum iron to transferrin. Represents proportion of transferrin binding sites occupied by iron.
Diurnal fluctuations can be significant. Malnutrition and chronic disease decrease transferrin synthesis, while TSAT <16% suggest anaemia. TSAT increases in inflammation if iron levels are constant. This can be useful measurement for equivocal Ferritin levels due to inflammation.

Total Iron Binding Capacity (TIBC): The maximum amount of iron that can bind to transferrin (increases when iron is deficient). Derived from transferrin levels
Unsaturated Iron-Binding Capacity (UIBC): The concentration of free sites on transferrin
Soluble Transferrin Receptor: Membrane-bound transferrin receptor levels increase in iron deficiency. Released into plasma. Raised levels may indicate advanced iron deficiency.
Zinc Protoporphyrin: Outdated test.
Hepcidin: Decreased in iron deficiency, increased in inflammation. Expensive test, no advantages over alternatives.

Iron is not recommended as a standalone measure to assess iron deficiency
Transferrin delivers iron to tissues, is a useful measure of iron availability when with other markers (like ferritin or FBC/reticulocyte parameters).
Don't substitute Transferrin Saturation for other transferrin-based measurements
Current guidelines do not recommend extensive tests due to limited clinical value.