ferroxidase

Ferroxidase refers to enzymes that catalyze the oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+), typically using molecular oxygen as the oxidant. These enzymes are usually multicopper oxidases, which contain copper centers that shuttle electrons during catalysis. The core biochemical transformation is Fe2+ → Fe3+, enabling iron to participate in cellular transport and storage processes that require ferric iron, such as loading onto transferrin in plasma or export from cells.

Common ferroxidases include ceruloplasmin, a multicopper protein in blood plasma, which oxidizes Fe2+ to Fe3+ for efficient iron binding to transferrin. In the intestinal epithelium, hephaestin functions alongside ferroportin to promote iron efflux by oxidizing Fe2+ to Fe3+, facilitating loading onto transferrin during intestinal absorption. In yeast and some fungi, the high-affinity iron uptake system comprises the ferroxidase Fet3p paired with iron permeases; Fet3p oxidizes Fe2+ to Fe3+, enabling iron transport into the cell. Plants possess ferroxidases, such as members of the FRO (ferric chelate reductase oxidase) family, that participate in iron uptake and homeostasis in roots and other tissues.

Structural and mechanistic features include the presence of multiple copper centers arranged in distinct domains, which enable electron transfer from iron substrates to oxygen. This class of enzymes plays a crucial role in iron homeostasis, facilitating iron mobilization, transport, and storage, and its dysfunction can contribute to disorders of iron metabolism. Clinically, mutations in ceruloplasmin cause aceruloplasminemia, a neurodegenerative disorder characterized by brain iron accumulation.