Role of albumin's copper binding site in copper uptake by mouse hepatocytes.
It is possible, in vitro, to label albumin with copper either exclusively on the specific binding site or partly on the specific site and also on other sites by altering the pH at which the two ligands are mixed. Copper attached exclusively to the specific site is taken up more rapidly than copper attached to that site and others on albumin. The effect is proportional to the amount of copper on the specific site. Additional histidine stimulates uptake irrespective of the copper binding site on albumin. The effect is related to the histidine on position 3 of the albumin, since it is not seen when dog albumin is labeled under the same conditions. The data suggest that the cell recognizes and presumably binds the copper-albumin (CuAlb) complex but may preferentially recognize the ternary complex formed by CuAlb and histidine. We suggest that, in vivo, copper is bound mainly as the ternary complex and that the structure formed, presumably similar to that formed by a copper-histidine complex, is what is actually recognized by the cell. After binding, the albumin and histidine are released, possibly by a reduction step, and the copper is transported across the membrane. If the copper cannot be transported (as occurs when the cells are incubated at 4 degrees C), it blocks further binding of the ternary complex.
McArdle
H J
HJ
Scobie and Claire Mackinnon Trace Element Research Group, Murdoch Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
Gross
S M
SM
Danks
D M
DM
Wedd
A G
AG
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006639:Histidine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism*
D012709:Serum Albumin; D006639:Histidine; D003300:Copper