The determination of ceruloplasmin
In 1948, Holmberg and Laurell1 isolated from human serum the blue copper-containing ·a-globulin ceruloplasmin. The molecular weight of this protein is approximately 151,000, and the copper content 0·34 per cent, which corresponds to eight atoms of copper per molecule. Ceruloplasmin possesses in vitro oxidase activity towards, for example, epinephrine2•3, 5-hydroxytryptamine4, dihydroxyphenylalanine2, p-phenylenediamine5 and N,N-dimethyl-p-phenylenediamine (DPP) 6• The present view is that 90-95 per cent of serum copper is tightly bound in ceruloplasmin 7• 8 • This is based principally on the fact that variations in copper and ceruloplasmin concentrations are almost always in step with one another. lt is thus conceivable that the enzyme plays an important röle in copper metabolism. The exact nature of its function has not yet been elucidated, however. It has been reported that the concentrations of copper and of ceruloplasmin in serum are greatly increased in late pregnancy and in many diseases, e.g. bacterial infections, neurological disorders, cirrhosis, hepatitis and acute and chronic leukaemia 7 ; while in Wilson's disease the concentration of ceruloplasmin is greatly reduced. Akersfeldt's report6 of an increased ceruloplasmin concentration in the sera of patients with mental diseases aroused great interest. Some investigators were able to reproduce Akersfeldt's results, but many others were not. In our opinion, however, the methods used, all based on the measurement of the oxidase activity of serum; were not optimal. With a modified method, we have also been unable to find any deviation from normal as described by Akersfeldt. However, a positive correlation was found between age and ceruloplasmin concentration. Our material comprised subjects whose ages ranged from 20 to 60 years9• In another series of experiments, a positive correlation between age and total copper in serum was established, as would be expected on the basis of the above-mentioned relationship. The concentration in females was significantly higher than in males for all ages. Again our experiments were carried out with subjects in the age group from 20 to 60 yearsl 0 • It is generally accepted that ceruloplasmin is the only oxidase in human serum, and that ceruloplasmin copper • accounts for all tightly-bound serum copper. Deutsch recently published ~ direct method for the measurement of ceruloplasmin11• This prompted lflS to test these concepts. The first results of these experiments are report~d here. Oxidase activity, ceruloplasmin and .total copper were determined in sera obtained from normal males and male patients with a variety of ciinical conditions after overnight fasting. For the measurement of oxidase activity,