Deakin University

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Copper is taken up efficiently from albumin and α2-macroglobulin by cultured human cells by more than one mechanism

journal contribution
posted on 2008-09-01, 00:00 authored by M Moriya, Y H Ho, A Grana, L Nguyen, A Alvarez, R Jamil, Leigh Ackland, Agnes MichalczykAgnes Michalczyk, P Hamer, D Ramos, S Kim, Julian MercerJulian Mercer, M Linder
Ionic copper entering blood plasma binds tightly to albumin and the macroglobulin transcuprein. It then goes primarily to the liver and kidney except in lactation, where a large portion goes directly to the mammary gland. Little is known about how this copper is taken up from these plasma proteins. To examine this, the kinetics of uptake from purified human  albumin and α2-macroglobulin, and the effects of inhibitors, were measured using human hepatic (HepG2) and mammary epithelial (PMC42) cell lines. At physiological concentrations (3–6 µM), both cell types took up copper from these proteins independently and at rates similar to each other and to those for Cu-dihistidine or Cu-nitrilotriacetate (NTA). Uptakes from   α2-macroglobulin indicated a single saturable system in each cell type, but with different kinetics, and 65–80% inhibition by Ag(I) in HepG2 cells but not PMC42 cells. Uptake kinetics for Cu-albumin were more complex and also differed with cell type (as was the case for Cu-histidine and NTA), and there was little or no inhibition by Ag(I). High Fe(II) concentrations (100–500 µM) inhibited copper uptake from albumin by 20–30% in both cell types and that from {alpha}2-macroglobulin by 0–30%, and there was no inhibition of the latter by Mn(II) or Zn(II). We conclude that the proteins mainly responsible for the plasma-exchangeable copper pool deliver the metal to mammalian cells efficiently and by several different mechanisms.α2-Macroglobulin delivers it primarily to copper transporter 1 in hepatic cells but not mammary epithelial cells, and additional as-yet-unidentified copper transporters or systems for uptake from these proteins remain to be identified.



American journal of physiology: cell physiology






708 - 721


American Physiological Society


Bethesda, Md.







Publication classification

C1 Refereed article in a scholarly journal; C Journal article

Copyright notice

2008, American Physiological Society