Other Copper-Binding Proteins

As is the case for other copper-binding proteins, the ligands are further oriented by hydrogen bonding to neighboring atoms. There is a local twofold axis relating the Cu(A) and Cu(B) sites of hemocyanin ... 

Recent publications signal the continued interest in the function of this protein. It has been called a stress enzyme, involved in influenza virus infection (Tomas and Toparceanu, 1986). An explanation for Wilson s disease in terms of a genetic defect resulting in failure to convert from a neonatal (i.e., low) level of ceruloplasmin and copper to a normal adult level has been reported (Srai et al., 1986). Tissue specificity for the binding of ceruloplasmin to membranes was demonstrated in a study investigating the possible role of ceruloplasmin-specific receptors in the transfer of copper from ceruloplasmin to other copper-containing proteins (Orena et al, 1986). Ceruloplasmin has been shown to be effective in transferring copper to Cu,Zn-SOD in culture (Dameron and Harris, 1987), as has copper albumin. In view of the variable content of copper in this protein, it is not clear which copper is transferred. 

Hypoproteinemia may result in low levels of serum calcium, ceruloplasmin, and transferrin. Because losses of iron are at most 0.5-1.0 mg/24 hr, even with the heaviest proteinuria, other factors must operate to produce iron deficiency and microcytic hypochromic anemia. Although the copper-binding protein ceruloplasmin is lost in the urine in nephrotic subjects and its plasma levels are low, plasma and red cell copper concentrations are usually normal. Zinc circulates mainly bound to albumin and also to transferrin, and thus the reported reduction zinc concentration in plasma, hair, and white cells in nephrotic patients is not surprising. 

Cadmium shares chemical properties with zinc and mercury, but in contrast to mercury, it is incapable of environmental methylation, due to the instability of the monoalkyl derivate. Similarities and differences also exist in the metabolism of Zn, Cd, and Hg. Metallothioneins and other Cd-binding proteins hold or transport Cd, Zn, and Hg within the body. Metallothioneins are metal-binding proteins of relatively low molecular mass with a high content of cysteine residues that have a particular affinity for cadmium, as well as for zinc and copper, and can affect its toxicity. 

Physiological free copper concentrations are certainly decisive for determining a role for copper in PrP cellular function. It is important to recall the properties of Cu2+ in buffer solution. The solubility product (Ksp) of Cu(OH)2 at physiological pH is in the order of 10 20. i.e., rather small. It is therefore likely that it is bound to other compounds like, e.g., human serum albumin which binds copper in the picomolar range [92]. To evaluate whether PrP is a functional copper binding protein one has to determine the relative concentration of membrane attached PrPc and that of albumin in the cerebrospinal fluid which is about 3 pM [93]. However, the free concentration of copper has not been determined. Inside cells... 

---