Iron metabolism !

The body has no way to excrete iron: it controls how much it absorbs with hepcidin, carries it on transferrin and stores it in ferritin.

Updated 2026-11-01

Key facts

An adult has 3–4 g of iron; about two thirds is in hemoglobin.
Only 1–2 mg a day is absorbed in the duodenum, the same as is lost; nearly all daily iron (20–25 mg) comes from macrophages recycling old red cells.
Hepcidin (liver) blocks ferroportin, the only exit door for iron from cells: absorption falls and iron is trapped in macrophages.
Ferritin: the store and best marker of reserves (low = deficiency), but it rises with inflammation because it is an acute-phase reactant.

Absorption: in the duodenum, duodenal cytochrome b reduces dietary Fe³⁺ to Fe²⁺ and the DMT1 transporter carries it into the enterocyte; heme iron enters by another route and heme oxygenase releases it.
Exit: ferroportin moves it out across the basal side; hephaestin (and ceruloplasmin in plasma) oxidises it to Fe³⁺ so transferrin can take it.
Transport: each transferrin carries two Fe³⁺; it is normally 20–45 % saturated. Cells take it up through transferrin receptor 1 and endocytosis; in the acidic endosome the iron is released.
Storage: ferritin holds up to about 4500 iron atoms in its shell; hemosiderin is degraded ferritin in lysosomes, typical of overload.
Cell control: when iron is low, IRP proteins bind the mRNA IREs: they block translation of ferritin and ALAS2 (5' IRE) and protect transferrin receptor mRNA (3' IRE).
Whole-body control: hepcidin rises with iron excess and inflammation (IL-6); it falls with iron deficiency, hypoxia and active erythropoiesis (erythroferrone).
Vitamin C and heme iron improve absorption; phytates, tannins in tea and coffee, and calcium reduce it.

Iron deficiency: low ferritin, high transferrin (TIBC), low saturation; it is the most common cause of anemia worldwide.
Anemia of inflammation: high hepcidin traps iron; normal or high ferritin with low serum iron and low TIBC.
Hereditary hemochromatosis: low hepcidin lets too much iron in; high transferrin saturation (over 45 %) and high ferritin.
Repeated transfusions (thalassemia, sickle cell anemia) cause iron overload because there is no way to excrete it.

Think of the answer, then tap the question to see it.

Which protein does hepcidin act on, and with what effect?

It binds ferroportin and causes its degradation: intestinal absorption and iron release from macrophages fall.

How do labs distinguish iron deficiency from anemia of inflammation?

In deficiency ferritin is low and TIBC high; in inflammation ferritin is normal or high and TIBC low.

What does IRP do when the cell is short of iron?

It binds the IREs: it blocks ferritin synthesis and stabilises transferrin receptor mRNA to take up more iron.

What is the main daily source of iron for making hemoglobin?

Iron recycled from old red cells by macrophages (20–25 mg a day), far more than the diet.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Reactome | Iron uptake and transport (Reactome, 2026); HAMP gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Ferritin blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Total iron binding capacity: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); TF: Serotransferrin (human) (UniProt, 2026); Iron: MedlinePlus (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.