Regulation of iron balance

The main cells implicated in systemic iron regulation are enterocytes, which absorb non-heme iron from the diet through DMT1; hepatocytes, which produce hepcidin according to the iron concentration; and macrophages, which release iron during the breakdown of hemoglobin from senescent red blood cells. Ferroportin exports iron from all of these cells into the circulation with the cooperation of a ferroxidase (hephaestin in enterocytes and ceruloplasmin [CP] in macrophages and hepatocytes) that oxidizes Fe²⁺ to Fe³⁺.

(A) In iron deficiency there is increased iron absorption and recycling. Absorption of iron by enterocytes is facilitated by duodenal cytochrome b (DYCTB), an iron reductase. Hepcidin synthesis is suppressed. Ferroportin is free to export iron from macrophages and enterocytes, after which iron is bound to transferrin.

(B) In iron overload there is reduced iron absorption and recycling. Hepcidin production is high; its synthesis is stimulated by BMP6, which is induced by increased liver iron. Hepcidin released into the circulation binds ferroportin, and the complex is internalized and degraded, in turn blocking iron export into the circulation.