The nature of the copper complexes in bile and their relationship to the absorption and excretion of copper in normal subjects and in Wilson's disease

Abstract

SUmmARY Copper in bile has been shown by electrophoresis to occur neither as free ions nor complexed to protein but to be associated with a component of the micellar complexes of bile. Solvent fractionation studies suggest that the bile salt components of the lecithin-bile salt complexes are the active binding agents. The effects of specific bile salts on the behaviour of copper during electrophoresis supports this possibility.The relationship of certain bile salts to the excretion of copper in man during the time that an external biliary fistula was functioning and to the intestinal absorption of copper in the rat was found to confirm this concept.

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

“…We believe that this newly described activity of bilirubin may be of physiological importance. In humans, bile clearly represents the major physiological excretory fluid for both conjugated bilirubin (1) and copper (20), and the concentrations of copper used in our experiments are well within the range of biliary copper reported (20,(27)(28)(29)(30). Unlike most biological tissues, in which transition metals are either part of the active site in enzymes or bound to specific transport or storage proteins, biliary copper does not seem to be protein bound (20,(27)(28)(29).…”

“…1D), a physiological form of phospholipids 18:2-OOH was decomposed very rapidly in the presence of both BR-DT and cupric ion (Fig. 3) at concentrations found in normal bile and duodenal juice (4,20,(27)(28)(29)(30). To be able to follow the degradation of 18:2-OOH quantitatively, all reactions had to be carried out at 25TC rather than 37TC.…”

Elevated copper impairs hepatic nuclear receptor function in Wilson’s disease

“…WD patients with elevated hepatic copper have disrupted metabolic nuclear receptor signaling. Aside from findings of decreased biliary copper excretion (32,33) without pathological changes in total bile acids (34), there are a limited number of studies regarding bile acid metabolism in WD patients. To address whether WD patients exhibit changes similar to those seen in the WD mouse model, we measured nuclear receptor target gene mRNA expression and activity in adult hepatic autopsy samples obtained from the National Disease Research Interchange (NDRI).…”

Impaired Hepatic Copper Homeostasis in Long-Evans Cinnamon Rats: Reduced Biliary Excretion of Copper

“…They include 1 ) synthesis of abnormal protein with high coppcr binding activity (29). 2 ) persistent fetal mode of copper metabolism (30) on the basis of the concept of a lysosomal defect in hepatocytes, 3) absence or defect ofthe putative carrier proteins in the hepatocyte required for incorporating copper into ceruloplasmin or excreting copper by way of the bile (6,31), and 4) deficiency of copperbinding protein in bile (32)(33)(34), probably the protein identical to serum ceruloplasmin (34). It is also reported that normal human bile contains two molecular forms of ceruloplasmin.…”