Human iron metabolism

Iron is an essential nutrient for human beings, although it can also be toxic. The most important role is in the heme protein of hemoglobin and cytochrome P-450, and secondarily for myoglobin, which transports oxygen into muscle cells. Iron also is a component of a number of enzymes.

Control mechanisms for iron metabolism are not fully understood, but there is increasing opinion that a peptide hormone produced in the liver, hepcidin, is the "master controller." Originally thought to be an antibacterial substance, it is now believed to be an inhibitor of iron intake into the body.

Requirements

The actual requirement for iron in food is quite low, as the body conserves iron stores.

Digestion

Iron, in food, is processed differently depending if it is in the form of heme (e.g., in meats) or in other molecules. As food breaks down in the stomach, ferric (Fe⁺³) iron is reduced to ferrous (Fe⁺²) iron by the enzyme ferric reductase. Ascorbic acid and other reducing agents stimulates the reduction, and thus stimulates absorption.

Non-heme iron, however, may not be available to the digestive processes. While spinach is legendary as an iron source, the iron in raw spinach is bound into a non-absorbable oxalate. Cooking the spinach does make the iron bioavailable; the cartoon character Popeye the Sailor Man was correct in eating his spinach from a can.

Most actual absorption takes place in the duodenum. Heme is absorbed via the heme transporter protein. Non-heme iron enters the apical surface of the enterocytes lining the duodenum via divalent metal transporter 1 (DMT1), carrying iron into the interstitial fluid by a protein called ferroportin (FP).

Hepcidin binds to ferroportin, inhibiting its action.

Distribution

Ferrous iron, in plasma, is reconverted to ferric, and bound to a carrier protein, ferritin.

Ferritin in plasma stays in equilibrium with ferritin in bone marrow, and plasma ferritin is indicative of actual iron stores in the marrow.

Disorders of iron metabolism

Not all anemia is due to disorders of iron metabolism, but iron deficiency anemia is a syndrome commonly seen, with many causes. Iron in excess through a metabolic error is less common, and called hemochromatosis. Among children in the U.S., iron supplements are the most common source of serious accidental poisoning.

Iron loading increases hepcidin synthesis (i.e., reducing iron intake), while hypoxia and anemia decrease its production.

Hepcidin is markedly induced during inflammation, trapping iron in macrophages, decreasing plasma iron concentrations, and contributing to the anemia of inflammation.