What happens at the molecular level in iron transport

In biological systems iron occurs in two oxidation states: as divalent iron (Fe²⁺) and as trivalent iron (Fe³⁺). The transition between these two forms matters for the orderly transport of the element in the body, because the transport protein transferrin binds trivalent iron only.

Copper in the role of oxidation catalyst

Ceruloplasmin, a copper-containing glycoprotein in blood plasma, catalyses the oxidation of Fe²⁺ to Fe³⁺. This process is known as ferroxidase activity. Six copper atoms are bound per ceruloplasmin molecule and take part in electron transfer. Without sufficient copper, ceruloplasmin cannot perform its ferroxidase function, and iron remains in the divalent form.

In the liver, copper is incorporated into the apoprotein apoceruloplasmin, from which the functional holoceruloplasmin arises. This assembly depends on copper availability in the hepatocyte.

From the enterocyte into the blood plasma: the task of the ferroxidases

In the intestine, iron from food is taken up by the enterocytes. Export from the cell takes place via the membrane protein ferroportin. But before the iron can bind to transferrin, it must be oxidised. Hephaestin performs this task — a membrane-bound copper enzyme sitting on the basolateral side of the enterocyte. Hephaestin is structurally related to ceruloplasmin and likewise contains copper as a cofactor.

The copper-mediated oxidation step is therefore decisive at two anatomically different places: in the intestinal epithelium (hephaestin) and in blood plasma (ceruloplasmin).

A trace element with a documented contribution to iron balance

Copper (chemical symbol Cu, from the Latin cuprum) is one of the essential trace elements. The human body contains a total of roughly 80–120 mg of copper, with the highest concentrations found in the liver, brain and kidneys.

The European Food Safety Authority (EFSA) has scientifically assessed the relationship between copper and normal iron transport in the body. On the basis of this assessment, the EU Commission has authorised a health claim based on the contribution of copper to iron transport.

Biochemically, this contribution can be traced back to the ferroxidase activity of copper-containing enzymes, described in detail above and in the guide.