Copper protein damage

De Vos et al. (1989) suggest that the copper-induced damage to the permeability barrier in roots of Silene cucubalus is caused by a direct metal action on both membrane lipids and thiols. They propose that the first damaging effects of copper ions is the oxidation and cross-linking of membrane protein sulphydryls. However, they also adjudge an important role to the copper induced membrane lipid peroxidation, possibly due to direct free radical formation in the membrane this effect could be enhanced by a depletion of thiols such as glutathione which results in a concomitant decrease of the cellular defence system against free radicals. 

The basic defect in this disease appears to be in the interaction of copper with the carrier protein caeruloplasmin to which it normally binds strongly. In many of the victims caeruloplasmin levels are low and an abnormally large amount of copper is weakly bound to serum albumin. However, some disease-free heterozygotes also have low levels of caeruloplasmin, while a minority of homozygotes have both normal caeruloplasmin levels and Wilson s Disease. The loss of copper in bile is often lower than normal and a metallothionein-like copper protein may be induced in the liver, perhaps causing the copper retention. An increased copper uptake firom the diet may also occur. Renal damage arises in the later stages of Wilson s disease, perhaps caused in part by the accumulation of a copper-metallothionein. 

Superoxide Dismutase. This enzyme catalyzes the dismutation of superoxide [13]. For optimal enzymatic activity, at least two of the protein s four metal ions must be cupric. This copper protein isolated from various sources was found to have an isoelectric point of 4.74-4.76 and an approximate molecular weight of 32000. High amounts of superoxide radical are generated through various enzymatic reactions. Superoxide dismutase may have a vital role in protecting the cell from damaging effects of the superoxide radical. The superoxide radical reduces cytochrome oxidase, which indicates the necessity for the removal of this anion to prevent fixation of the enzyme in the reduced state. 

The role of Cu as an essential trace element has focused attention on possible roles for copper chelation of biologically active ligands, with subsequent interference of normal transport and distribution, as well as the role of the metal in redox reactions due to the accessible oxidation states of (I) and (II). Similarly, the physiological response of copper levels in disease conditions [50] and the overall role of trace metals in health and disease [51, 52] are relevant and of considerable importance. The increase in serum copper content in infections, arthritic diseases, and certain neoplasms is well documented and, in fact, the subsequent decrease in level upon treatment has been used successfully as an indicator of cancer remission [50]. Copper complexes may be effective in therapy due in part to their ability to mimic this physiological response of elevated copper [53] and, clearly, the interplay of introduced copper with pre-existent bound copper and effects on copper—protein mediated processes will affect the ultimate biological fate of the complex. Likewise, while the excess accumulation of free Cu, and indeed Fe and Zn, caused by malfunction or absence of normal metabolic pathways is extremely damaging to the body, the controlled release of such metals may be beneficially cytotoxic. The widespread pharmacological effects of copper complexes have been briefly reviewed [54]. 

An excess of zinc will cause problems in humans. Excessive doses can lead to biochemical control system damage, while doses slightly higher than optimal can cause disorders in iron and copper metabolism, resulting in incurable anemia, decrease in activity of zinc protein enzymes, and pancreas and kidney damage (Boularbah et ah, 1999 Seiler et ah, 1994). Increased levels of zinc have been observed in nuclei of neoplastic cells and in cases of acute dental caries, however its role in these diseases has not been explained. 

Nishikawa T, Lee IS, Shiraishi N, Ishikawa T, Ohta Y, Nishikimi M. 1997. Identification of SlOOb protein as copper-binding protein and its suppression of copper-induced cell damage. J Biol Chem... 

Shiraishi N, Nishikimi M. 1998. Suppression of copper-induced cellular damage by copper sequestration with SlOOb protein. Arch Biochem Biophys 357(2) 225-230. 

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