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Radioactive leucine was administered to male Sprague-Dawley rats in order to measure the rate of release and decay of newly synthesized apoceruloplasmin and holoceruloplasmin in copper-deficient and normocupremic rats, respectively. Anticeruloplasmin antisera were used to isolate the protein from rat plasma. In copper-deficient rats the release of apoceruloplasmin into the circulation proceeded at the same rate as that of the copper-containing protein in normocupremic rats, although the concentration of apoceruloplasmin in copper-deficient rats was only 25% that of normal. This reduction was accounted for by the more rapid disappearance of apoceruloplasmin from the circulation. When copper was administered to copper-deficient rats no increase in the rate of release of either newly synthesized ceruloplasmin or preformed ceruloplasmin was observed, although the ceruloplasmin oxidase concentration rose over 8-fold by 8 hours. This rise was accounted for by the enhanced stability of the copper-containing protein. When 64Cu was administered to copper-deficient rats none of it was bound to circulating apoceruloplasmin, indicating that copper bound to the protein before it was released into the circulation.
Holtzman et al. (1970) studied this question.