Fig. 3. Hypothetical representation of cellular copper uptake pathways in fish, combining data from gill and intestine. See text for more details. Briefly, in the gills, cupric copper is probably reduced to Cu⁺ and enters via either a putative epithelial sodium channel (EnaC) or copper transporter 1 (CTR1). Metallochaperones (MC) bind Cu⁺ and guide it to the Golgi network (GN), where it is transported into the Golgi lumen via a MNK-`like' Cu⁺-ATPase. Cu⁺ is incorporated into metal binding proteins (MBP) within the GN. GN vesicles then traffic the copper to the basolateral membrane for release via exocytosis. Other ATPases on the basolateral membrane exporting copper (i.e. Ag⁺/Cu⁺-ATPase) may also be present. In the intestine, apical entry is presumed to be passive. Intestinal export may be via a Cu/Cl^- symporter, or via the MNK pathway described above. Excess copper is bound to low molecular mass proteins, such as metallothionein (MT). Li, aquatic ligand; MNK, Menkes Cu⁺-ATPase; CR, copper reductase.