Abstract

Ceruloplasmin is an abundant serum glycoprotein containing greater than 95% of the copper found in the plasma of vertebrate species. Although this protein is known to function as an essential ferroxidase, the role of ceruloplasmin in copper transport and metabolism remains unclear. To elucidate the role of ceruloplasmin in copper metabolism, the kinetics of copper absorption, transport, distribution, and excretion were examined utilizing (64)Cu in wild-type and aceruloplasminemic mice. No differences in gastrointestinal absorption, hepatic uptake, or biliary excretion were observed in these animals. Furthermore, steady state measurements of tissue copper content utilizing (64)Cu and atomic absorption spectroscopy revealed no differences in the copper content of the brain, heart, spleen, and kidney. Consistent with these findings, the activity of copper-zinc superoxide dismutase in these tissues was equivalent in wild-type and ceruloplasmin-deficient mice. Hepatic iron was elevated 3.5-fold in aceruloplasminemic mice because of the loss of ferroxidase function. Hepatic copper content was markedly increased in aceruloplasminemic mice. As no differences were observed in copper absorption or biliary copper excretion, these data suggest that in these animals, hepatocyte copper intended for ceruloplasmin incorporation is trafficked into a compartment that is less available for biliary copper excretion. Taken together, these data reveal no essential role for ceruloplasmin in copper metabolism and suggest a previously unappreciated complexity to the subcellular distribution of this metal within the hepatocyte secretory pathway.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.