Intracellular distribution of hepatic copper in normal and copper-loaded sheep.

This investigation was conducted to determine the intracellular distribution of copper in the liver of normal sheep, and the changes associated with exposure to increased dietary copper. Normal rat liver (3.8 + 1.0) ~/g Cu/g liver, wet tissue basis) and normal sheep liver (102.0 -+ 37.2 /~g Cu/g liver) was processed to give the four common subcellular fractions. When the intracellular distribution of copper in the two species was compared, the cytosol fraction of sheep liver contained a much lower (P<.001) percentage of copper than normal rat liver. Although the debris fraction of sheep contained a higher (P<.001) percentage than the rat, this copper did not appear to be associated with any specific component of this fraction. Feeding a high level of dietary copper to sheep elevated hepatic copper concentration (238.5 -+ 84.2 /~g Cu/g liver) significantly (P<.05). Comparison with the normal group showed that with the higher liver copper concentration, proport ionally less (P<.05) of the copper was found in the large granule fraction while proport ional ly more (P<.05) was present in the cytosol. These changes in the intracellular copper distribution of copper-stressed sheep directly oppose what is known for copperstressed rats. (