COMPARISON OF PATHWAYS OF COPPER-METABOLISM IN AORTA AND LIVER - A FUNCTIONAL TEST OF METALLOTHIONEIN

Soluble fractions from chick liver and aorta were examined for Cu-binding proteins. In liver a Zn-binding thionein appeared to be the major binding protein for Cu. Aortic tissue contained only traces of this thionein protein. Unlike liver, moderate amounts of soluble Cu in aorta showed no association with macromolecules. Chicks fed on Cu-deficient diets for 8 days had 1/3 the liver concentrations of controls. Aortic Cu concentration was decreased only slightly, but the activity of lysyl oxidase, a Cu-dependent enzyme in aorta, was decreased significantly. Treating the deficient chicks with CuSO4 (1 mg/kg) restored liver Cu rapidly. The increase correlated with the binding of Cu to a 10,000 MW component in the soluble fraction. Aortic Cu concentrations responded much less to the CuSO4 treatment, but lysyl oxidase activity was again measurable in the tissue. Radioactive isotopes of Cu bound almost exclusively to the 10,000 MW component in liver and to components of MW 30,000 or above in aorta. Hardly any of the administered radioactivity appeared with the 10,000 MW components in aorta, and none was found with unbound Cu. The 30,000 MW components in aorta showed superoxide dismutase activity that was sensitive to NaCN. They also showed the highest specific activity of Cu of any other aorta component. A clear distinction was seen between the metabolism of Cu in liver and aortic tissues. Whereas a Cu thionein, metallothionein, was a major component in the liver pathway, it is doubtful that this protein plays a major role in the intracellular metabolism of Cu in aortic tissue.