Effects of albumin and histidine on kinetics of copper transport by fibroblast

The kinetics of copper transport by fibroblasts were examined and compared with earlier data with hepatocytes to determine the basis of rapid, preferential copper uptake by the liver. The K(m) and maximal velocity (V(max)) parameters for copper transport by fibroblasts in serum-free media were comparable to the parameters with hepatocytes. As with hepatocytes, albumin markedly inhibited initial rates of copper transport by fibroblasts. Although the only effect of histidine on copper transport by hepatocytes in serum-free media is a small increase in K(m), histidine as His₂Cu decreases the V(max) of copper transport fivefold with fibroblasts. Moreover, although histidine increases copper accumulation by hepatocytes when transport is inhibited by albumin, histidine further inhibits copper accumulation by fibroblasts when albumin is in the medium. Thus the inhibitory effects of histidine and albumin on copper transport by fibroblasts are additive. The data are consistent with an intermediary role for the His₂Cu as the free ion, and copper transport is strictly passive with both cell types. The data suggest that rapid uptake by the liver is in part due to the ability of hepatocytes to transport copper from His₂Cu more rapidly than other cell types.