Ceruloplasmin, an Indicator of Copper Status

For clinical purposes, the non-ceruloplasmin copper fraction is routinely derived on the basis that ceruloplasmin binds six Cu atoms. However, this approach is limited because the actual ceruloplasmin copper binding is unclear. We performed direct measurement of the total serum copper and ceruloplasmin in 790 healthy individuals. We used an immunoprecipitation technique to separate ceruloplasmin and determined Cu content. With these values, we calculated the Cu/ceruloplasmin (Cp) ratio and thus generated data to support or discard the theoretical calculation of the non-ceruloplasmin fraction. Average of serum Cu and Cp levels were 18.4 +/- 4.4 micromol/l and 390 +/- 100 mg/l, respectively. The immunoprecipitation procedure allowed us to calculate a Cu/Cp ratio of 5.8, respectively, which supports the methodology of calculation that assigns a mean of six copper atoms to each ceruloplasmin molecule. With these values, we calculated that, in apparently normal adults, the non-ceruloplasmin copper (NCPC) fraction is lower than 1.3 micromol/l of Cu. In this report, we examine the Cp/Cu ratio by using Cp immunoprecipitation procedure. Our in vitro and in vivo studies indicate that, as a mean, there are 5.8 atoms of Cu per Cp molecule and that <1.3 micromol/l of Cu would correspond to the NCPC.