ferroxidase

Ferroxidases catalyze the oxidation of Fe2+ to Fe3+, which is essential because only ferric iron (Fe3+) can bind transferrin for transport in plasma; ferrous iron (Fe2+) is toxic and generates reactive oxygen species via Fenton reactions. Key ferroxidases include: (1) Ceruloplasmin - a copper-containing plasma glycoprotein synthesized by the liver that facilitates iron efflux from cells (hepatocytes, macrophages) by oxidizing Fe2+ exported via ferroportin, allowing it to bind transferrin. In Wilson disease, ceruloplasmin is characteristically low, and copper accumulates in tissues (liver, brain, cornea - Kayser-Fleischer rings) while iron homeostasis can also be secondarily affected. Aceruloplasminemia, a rare genetic disorder, causes iron overload in the brain and liver due to loss of ferroxidase activity, leading to neurodegeneration and diabetes. (2) Hephaestin - a membrane-bound ferroxidase in intestinal enterocytes that works with ferroportin to enable dietary iron absorption into the bloodstream; mutations cause microcytic anemia (as seen in sla mice models). Clinically, understanding ferroxidase function ties together iron metabolism, copper metabolism, and disorders like Wilson disease, hemochromatosis, and anemia of chronic disease (where hepcidin degrades ferroportin, indirectly affecting ferroxidase-mediated iron export). This enzyme activity is a key link between iron and copper homeostasis, both high-yield topics for USMLE Step 1.