Studies with Radioactive Copper (64Cu and 67Cu); The Incorporation of Radioactive Copper into Caeruloplasmin in Wilson's Disease and in Primary Biliary Cirrhosis

Abstract

1. A comparison has been made of the handling of radioactive copper by patients with Wilson's disease, patients with primary biliary cirrhosis and a small control group. The object of this study has been to assess the influence of an expanded hepatic pool of copper on the incorporation of radioactive copper into caeruloplasmin. 2. Studies with 67Cu have shown that radioactivity disappears steadily from the plasma of patients with Wilson's disease for periods up to 296 h. Both in patients with primary biliary cirrhosis and in controls, a well-marked secondary rise occurs as radioactive copper is incorporated into caeruloplasmin. 3. Caeruloplasmin has been isolated from the serum of one control subject, one patient with primary biliary cirrhosis and one with Wilson's disease. Of the plasma radioactivity 90% was present in the caeruloplasmin of the control subject and the patient with primary biliary cirrhosis; only 27% was found in the caeruloplasmin of the patient with Wilson's disease. 4. Turnover time for liver copper has been determined; in the control subjects it was of the order of 20–30 days, in the patients with primary biliary cirrhosis it was between 600 and 700 days, in Wilson's disease the time exceeded 1800 days. In all cases the turnover time for radioactive copper was significantly less. 5. We conclude (a) that newly arrived radioactive copper is preferentially handled in the presence of copper overload and (b) dilution of radioactive copper in an expanded hepatic pool of the metal cannot alone account for the delayed incorporation found in patients with Wilson's disease.

Turnover Studies of Copper in Homozygotes and Heterozygotes for Wilson's Disease and Controls: Isotope Tracer Studies with 67Cu

“…Our homozygotes and heterozygotes also exhibited marked retention of 67Cu. Gibbs & Walshe (1971) reported calculated turnover times for liver 64Cu or 67Cu in four normal subjects and two patients with WD which were similar to total body turnover time of 67Cu in our subjects.…”

“…(c) Scheuer & Barka (1964) showed that copper loading in rats did not influence the hepatic uptake and biliary excretion of 64Cu. (d) Gibbs & Walshe (1971) have reported exceedingly long (639-2954 days) calculated turnover times for stable liver copper associated with calculated radioactive 64Cu or 67Cu hepatic turnover times of 105 and 204 days in patients with WD. This suggests that the 64Cu and 67Cu were not freely in equilibrium with all the hepatic (or body) copper.…”

Demonstration of an intracellular copper-binding protein by orcein staining in long-standing cholestatic liver diseases.

“…In extrahepatic cholestasis increased amounts of copper can be demonstrated only after several months of obstruction (Smallwood et al, 1971). Studies of copper kinetics with radioactive copper in patients with PBC have shown that unlike the findings in Wilson's disease, hepatic uptake, incorporation into caeruloplasmin, and plasma clearance are all normal (Gibbs and Walshe, 1971;Smallwood et al, 1971).…”

Esterase D and retinoblastoma gene loci are tightly linked to Wilson's disease in Chinese pedigrees from Taiwan

“…The basic defect is unknown, but it seems to involve the decreased biliary excretion of copper (Gibbs and Walshe 1980) and diminished incorporation of copper into the ceruloplasmin (Gibbs and Walshe 1971). Kinetic studies in the rat indicate that the functional pools of copper for ceruloplasmin production and for biliary excretion differ (Owen 1980).…”