A kinetic model of copper metabolism in sheep

Abstract

A three-compartment model was developed to provide a simple kinetic description of the metabolism of copper in six sheep with liver copper concentrations of 433¦51 ppm ( mean ¦ SD dry weight). This was achieved by measuring the radioactivity in samples of blood, liver, urine and bile as a function of time after the intravenous administration of c. 1.4 mCi of 64Cu. Sizes of compartments, flow rates and rate constants were evaluated and validated experimentally by measuring the excretion of copper in urine and bile and its accumulation in the liver. The model postulates two separate mechanisms for the handling of copper by the liver, and biliary copper excretion was not related to total liver copper content. The model was tested in sheep with a wider range of liver copper concentrations, and the copper in the two compartments (C2 and C3), attributed to liver, corresponded to the actual liver copper content when this was between 30 and 70 mg. The rate constants also responded consistently to increased liver copper status. Within the 'normal' liver copper range of 50-70 mg, the three-compartment model was closed but outside this range, the undefined parameter K03 was no longer zero. This response suggests that copper is moving from C2 and C3 to either supply tissue requirements or be redistributed in an additional storage compartment.