The effect of molybdenum and sulfur on the kinetics of copper metabolism in sheep

Abstract

Sheep were given 0, 5, 10, 15 or 25 mg/day molybdenum with or without 1.1 g/day sulfur orally for 1 week, and the nature of the interaction between these elements and copper was then investigated by injecting 64Cu intravenously, and analysing the disappearance of 64Cu from the blood by compartmental analysis. Molybdenum treatment decreased the rate of disappearance of 64Cu from the blood, and this decrease was enhanced by the concurrent administration of sulfur. Analysis of the disappearance curves in terms of a three-compartment catenary model showed that calculated total liver copper pool size (mean¦s.d. (n = 4)) was decreased from 37.5¦6.4 mg (no treatment) to 6.3 ¦ 1.9 mg (50 mg/day molybdenum plus sulfur), whereas the liver copper pool size (determined by biopsy) remained unchanged. The reduction in calculated pool size was proportional to the molybdenum dose and was similar in magnitude to the reduction in actual copper pool size obtained following long-term (6 months) dosing with molybdenum and sulfur. These changes were most likely due to alterations in the kinetic parameters responsible for the initial phase of removal of 64Cu from the blood, i.e. K21 (the rate of transfer between blood copper (Q1)and liver copper (Q1 + Q2)), and bloodcopper. Consequently, therelationship between K21,various blood copper fractions and molybdenum dose rate was investigated using the results of this experiment and data obtained from the literature; it was found that a reduction in the amount of copper in the blood which exchanged freely with the 64Cu was the most likely explanation for the decrease in the rate of disappearance of 64Cu from the blood following molybdenum and sulfur treatment.