ceruloplasmin

Ceruloplasmin is a copper-containing glycoprotein synthesized by the liver and released into the bloodstream, where it serves as the major copper carrier and a multicopper oxidase. It binds the vast majority of plasma copper and acts as a ferroxidase, converting ferrous iron (Fe2+) to ferric iron (Fe3+) to enable iron binding to transferrin and proper iron export from cells.

Structure and synthesis: Ceruloplasmin is a large secreted protein, rich in N-linked glycosylation, and contains multiple copper centers essential for its enzymatic activity. Copper is incorporated during maturation in the liver, where the ATP7B copper-transporting ATPase facilitates delivery of copper into ceruloplasmin before secretion.

Functions: The ferroxidase activity of ceruloplasmin contributes to iron homeostasis and cellular iron efflux. In addition to its enzymatic role, ceruloplasmin has antioxidant properties and may participate in oxidative stress defense. As a plasma copper carrier, it stabilizes copper transport in the circulation.

Clinical significance: Ceruloplasmin levels and activity are used in evaluating disorders of copper metabolism. Aceruloplasminemia is a rare autosomal recessive disorder caused by CP gene mutations, leading to lack of ceruloplasmin and prominent iron accumulation in the brain, retina, and pancreas with neurological and metabolic manifestations. In Wilson disease, ceruloplasmin levels are often low due to impaired copper incorporation into the protein, although levels can be normal in some cases. Ceruloplasmin is also an acute-phase reactant, raising levels during inflammation, infection, or pregnancy.

Laboratory assessment commonly includes measurement of total ceruloplasmin concentration and ferroxidase (oxidase) activity, which together aid diagnosis and disease monitoring.