ferroxidases

Ferroxidases are enzymes that catalyze the oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+), an essential step in iron metabolism. The oxidation typically uses molecular oxygen as the electron acceptor, producing water as a byproduct. This conversion is important because Fe3+ is the form that binds to iron carriers such as transferrin and is ready for transport or storage.

Most well-characterized ferroxidases belong to the multicopper oxidase family. In humans, ceruloplasmin is a copper-containing plasma ferroxidase that supports iron export from transferrin-producing cells, while hephaestin is a membrane-associated ferroxidase that facilitates iron efflux in intestinal enterocytes. In yeast and other fungi, Fet3p serves as a ferroxidase component that works in concert with a permease to support iron uptake. In ferritin, the H-chain possesses ferroxidase activity that accelerates the oxidation of Fe2+ during mineral core formation, contributing to safe iron storage.

Ferroxidase activity is distributed across bacteria, plants, fungi, and animals, reflecting a conserved role in iron homeostasis. Plant systems also deploy ferroxidases to support iron uptake and distribution, including certain multicopper oxidases at the root or vascular tissues. Defects in ferroxidases such as ceruloplasmin or hephaestin can disrupt iron export, leading to iron misdistribution and conditions including neurodegenerative iron accumulation or iron-deficiency anemia.

Ferroxidases are related to, but distinct from, other multicopper oxidases; while they share catalytic features, their defining function is the oxidation of Fe2+ to Fe3+.