Copper transport and metabolism are normal in aceruloplasminemic mice

Ceruloplasmin is an abundant serum glycoprotein containing greater than 95% of the copper found in the plasma of vertebrate species. Although this pro tein is known to function as an essential ferroxidase, the role of cerulopl asmin in copper transport and metabolism remains unclear. To elucidate the role of ceruloplasmin in copper metabolism, the kinetics of copper absorpti on, transport, distribution, and excretion were examined utilizing Cu-64 in wild-type and aceruloplasminemic mice. No differences in gastrointestinal absorption, hepatic uptake, or biliary excretion were observed in these ani mals. Furthermore, steady state measurements of tissue copper content utili zing Cu-64 and atomic absorption spectroscopy revealed no differences in th e copper content of the brain, heart, spleen, and kidney. Consistent with t hese findings, the activity of copper-zinc superoxide dismutase in these ti ssues was equivalent in wildtype and ceruloplasmin-deficient mice. Hepatic iron was elevated 3.5-fold in aceruloplasminemic mice because of the loss o f ferroxidase function. Hepatic copper content was markedly increased in ac eruloplasminemic mice. As no differences were observed in copper absorption or biliary copper excretion, these data suggest that in these animals, hep atocyte copper intended for ceruloplasmin incorporation is trafficked into a compartment that is less available for biliary copper excretion. Taken to gether, these data reveal no essential role for ceruloplasmin in copper met abolism and suggest a previously unappreciated complexity to the subcellula r distribution of this metal within the hepatocyte secretory pathway.