title: ATP-dependent copper transporter, in the Golgi apparatus of rat hepatocytes, transports Cu(II) not Cu(I).
abstract: The Wilson disease adenosinetriphosphatase (ATPase; ATP7B) is believed to bind copper as Cu(I). We provide evidence to suggest that the ATPase actually transports Cu as Cu(II). When the copper is presented to rat liver microsomes as Cu(I), virtually all uptake is ATP independent. If the copper is presented as copper oxalate [Cu(II)], total uptake is reduced to approximately 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 override the effect of oxalate. The data indicate that there are two transporters in the microsomes, an ATP-independent Cu(I) transporter and an ATP-dependent Cu(II) pump. The activity of the Cu(I) transporter correlates most strongly with alkaline phosphatase, suggesting that it is derived from plasma membrane contamination. Cu(II) ATP-dependent transport correlates only with beta-1, 4-galactosyltransferase, which indicates that it is located in the Golgi apparatus.
authors.affiliation: Department of Child Health, Ninewells Hospital and Medical School, University of Dundee, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bingham
authors.forename: T J
authors.initials: TJ
authors.lastname: Ong
authors.forename: W J
authors.initials: WJ
authors.lastname: Ingledew
authors.forename: H J
authors.initials: HJ
authors.lastname: McArdle
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D002458:Cell Fractionation; D003300:Copper / Q000378:metabolism*; D003301:Copper Radioisotopes; D000073840:Copper-Transporting ATPases; D003570:Cytidine Triphosphate / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004734:Energy Metabolism; D005978:Glutathione / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010618:Phenanthrolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012044:Regression Analysis; D014544:Uridine Triphosphate / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003301:Copper Radioisotopes; D010618:Phenanthrolines; D014810:Vitamin E; D003570:Cytidine Triphosphate; D003300:Copper; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; C002478:bathocuproine; D000469:Alkaline Phosphatase; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases; D005978:Glutathione; D001205:Ascorbic Acid; D014544:Uridine Triphosphate