Effect of copper loading of preruminant calves on intracellular distribution of hepatic copper, zinc, iron, and molybdenum.

The subcellular distribution of Cu, Zn, Fe, and Mo was investigated in liver homogenates from preruminant calves fed control Cu (10 ppm), high Cu (1000 ppm), or high Cu plus high Zn (1000 ppm) milk replacer. For controls, Cu was located primarily in the nuclei and large granule fractions, Zn mainly in the cytosol, and Fe in the cytosol and nuclei fraction; Mo was present in all compartments but least in microsomes. Calves fed high Cu had markedly increased hepatic Cu concentration in the nuclei and cytosol fractions, reduced cytosol Zn, increased nuclei Fe, and decreased Mo concentration in all cell compartments. Feeding high Zn with high Cu (which prevented deaths from high Cu) reversed some changes in hepatic trace element patterns caused by high Cu while initiating new alterations. The marked increase in hepatic Cu and reduced Mo in nuclei and cytosol after Cu loading indicate that these compartments may have a predominant role in the development of Cu toxicity in the preruminant calf.