ATP-DEPENDENT COPPER TRANSPORTER, IN THE GOLGI-APPARATUS OF RAT HEPATOCYTES, TRANSPORTS CU(II) NOT CU(I)

The Wilson disease adenosinetriphosphatase (ATPase; ATP7B) is believed to bind copper as Cu(I). We provide evidence to suggest that the ATPa se actually transports Cu as Cu(II). When the copper is presented to r at liver microsomes as Cu(I), virtually all uptake is ATP independent. If the copper is presented as copper oxalate [Cu(II)], total uptake i s reduced to similar to 10% of Cu(I) levels, but ATP-dependent uptake rises, both as a proportion of total uptake and in absolute terms. The reducing agent vitamin C and the Cu(I) chelator bathocuproine both ov erride the effect of oxalate. The data indicate that there are two tra nsporters in the microsomes, an ATP-independent Cu(I) transporter and an ATP-dependent Cu(II) pump. The activity of the Cu(I) transporter co rrelates most strongly with alkaline phosphatase, suggesting that it i s derived from plasma membrane contamination. Cu(II) ATP-dependent tra nsport correlates only with beta-1,4-galactosyltransferase, which indi cates that it is located in the Golgi apparatus.