Copper proteins normal” complexes

Several copper enzymes will be discussed in detail in subsequent sections of this chapter. Information about major classes of copper enzymes, most of which will not be discussed, is collected in Table 5.1 as adapted from Chapter 14 of reference 49. Table 1 of reference 4 describes additional copper proteins such as the blue copper electron transfer proteins stellacyanin, amicyanin, auracyanin, rusticyanin, and so on. Nitrite reductase contains both normal and blue copper enzymes and facilitates the important biological reaction NO) — NO. Solomon s Chemical Reviews article4 contains extensive information on ligand field theory in relation to ground-state electronic properties of copper complexes and the application of... 

Type II Cu(II), or low-blue copper, is less colored at common research concentrations. These systems have received less attention than Type I copper. However, even low-blue cupric copper can possess high molar absorbtivities when compared with simple coordination complexes of Cu(II). The Cu(II) sites in such proteins also yield Azz values normally greater than 140 G, i.e., more like that of low molecular weight square planar Cu(II) complexes (2, 8). The only available crystal structure of a copper protein is that of a low blue protein bovine erythrocyte superoxide dismtuase (9). The two copper atoms in this protein are each coordinated to four histidine nitrogens in an approximate square planar array. 

The active sites of oxidized blue copper proteins are characterized by unique features relative to those of normal Cu(II) complexes. These features include an intense absorption... 

The normal range of serum copper in the adult is 11 to 24 Urinary copper is normally about 20 jjg/day. This level is equivalent to 0.5 to 3.0% of copper intake. Most of the copper absorbed into the body is excreted by way of the bile and lost via the feces. About 1.7 mg of copper is excreted in bile per day this amount varies with the amount absorbed from the diet. This copper occurs complexed with protein and bilirubin. Bilirubin is a catabolite of heme. The copper is excreted in the bile and lends not to be absorbed back Into the body, There is little or no enterohepatic circulation of copper. The concentration of bile copper drops markedly with a copper deficiency, contributing to the conservation of this mineral by the body. 

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]. 

Of course, this does not mean that the protein is unimportant for the structure of the active site in the blue copper proteins. A significant role of the protein is to restrict the number of ligands of the copper ion. Cu(I) complexes are usually four-coordinate and tetrahedral, while Cu(II) complexes normally are more or less six-coordinated (distorted octahedral). In fact, the unusual cupric structure in the blue copper proteins seems to be partly due to the simple fact that the copper ion is four-coordinated without any further axial ligands most optimized copper cysteinate models are far from square-planar unless the number of ligands is more than five. 

A number of copper-containing proteins show spectral features like those of normal copper complexes, and therefore do not appear to contain blue copper centres. Amongst these are galactase oxidase and the amine oxidases. It is noteworthy that it appears unlikely that the copper is involved in the activation of dioxygen. 

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