A mathematical model for copper metabolism and its relation to Wilson's disease

Abstract

-Radioactive copper has been used in studies of Cu metabolism by isolated perfused rat liver. The results suggested a model involving certain nonlinearities. The model postulates at least 3 distinct hepatic processes: preparation of Cu for excretion of the bile, temporary storage of Cu and incorporation of Cu Into ceruloplasmin with the final compartment involved In the production of labeled ceruloplasmin having limited capacity. When specific variations of this model were stimulated on an analog computer, deviations between theoretical and experimental values were within the range of experimental error. The liver storage compartment could provide an emergency means for removing ionic Cu from the blood, thereby preventing its toxic buildup in tissues. The storage compartment may normally represent an Intermediate product of ceruloplasmin synthesis which, if partially passed directly into the blood, would account for the biphasic appearance of labeled ceruloplasmin in blood and would be additional evidence for the previously reported heterogeneity of this fraction. Formulation of the mathematical model provides a compact integration of present information and a convenient means for testing additional hypotheses.