The Incorporation of Copper Into Ceruloplasmin in Vivo: Studies With Copper64 and Copper67*

The fact that absence or deficiency of the plasma copper-protein, ceruloplasmin, is almost always associated with the excessive deposits of tissue copper which characterize Wilsons disease has suggested that ceruloplasmin regulates copper absorption or excretion (1). Based on the in vitro demonstration of reversible dissociation of copper from ceruloplasmin, a hypothesis was proposed of how such regulation could be effected (2). This stated that if reversible dissociation of copper from ceruloplasmin occurred in the intes-tinal wall in vivo, a concentration of copper ions would result which could oppose the net transfer of copper ions from the intestinal lumen into the blood. The three experiments reported in this paper were designed to determine whether ex-change of ceruloplasmin copper for ionic copper, which is equivalent to reversible dissociation of ceruloplasmin copper, takes place in vivo. In the first experiment, exchange of cerulo-plasmin copper was looked for in patients with Wilsons disease in whom virtually no synthesis of the protein was occurring. The interpretation of this experiment required knowledge of whether the catabolism of ceruloplasmin was detectably different in a normal individual from its catabo-lism in patients with Wilsons disease. A com-parison of the half-life of ceruloplasmin, as one measure of its catabolism, was made in these two types of individuals in the second experiment. In the third experiment, the incorporation of ionic copper into ceruloplasmin was studied in an indi-vidual with normal copper metabolism in such a