Copper-containing enzyme functions

This discussion of copper-containing enzymes has focused on structure and function information for Type I blue copper proteins azurin and plastocyanin, Type III hemocyanin, and Type II superoxide dismutase s structure and mechanism of activity. Information on spectral properties for some metalloproteins and their model compounds has been included in Tables 5.2, 5.3, and 5.7. One model system for Type I copper proteins39 and one for Type II centers40 have been discussed. Many others can be found in the literature. A more complete discussion, including mechanistic detail, about hemocyanin and tyrosinase model systems has been included. Models for the blue copper oxidases laccase and ascorbate oxidases have not been discussed. Students are referred to the references listed in the reference section for discussion of some other model systems. Many more are to be found in literature searches.50... 

Pyrazole also causes, both in vitro and in vivo, a reduction in the activity of the mixed function oxidase enzyme system (B-79MI10504), and has also been used to inhibit the copper-containing enzyme monoamine oxidase in vitro, as have several related heterocyclic compounds (80MI10507) such as indazole (78), isoxazole (75) and benzothiazole (79). 

In in vitro studies penicillamine inhibited angiotensin-con-verting enzyme (ACE) and carboxypeptidase (930). Penicillamine interferes with the functions of the copper-containing enzyme ceruloplasmin, and some of the penicillamine- and copper-containing complexes formed in vivo have a superoxide dismutase effect (931). In patients with scleroderma, penicillamine normalized collagen metabolism, by inhibiting beta-galactosidase activity (932). 

Tyrosine, itself a degradation product of phenylalanine (Sec. 15.1), is initially converted to 3.4-dihydroxyphenylalanine (dopa), and the corresponding do pa quinone, by the copper-containing enzyme tyrosinase. Tyrosinase is found in melanocytes and is a mixed-function oxidase. It catalyzes the following reaction ... 

Copper is the third most abundant metallic element in the human body, following iron and zinc. It also occurs in all other forms of life and it plays a role in the action of a multitude of enzymes that catalyze a great variety of reactions. There are two cross-cutting ways to classify the copper-containing enzymes (1) According to the structural and spectroscopic characteristics of the copper complex at the active site. (2) According to the function of the enzyme. We shall base discussion on the first of these, with allusions to function as we go along. 

Examples of Copper-Containing Enzymes and Their Functions... 

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. 

Tire most studied of all copper-containing oxidases is cytochrome c oxidase of mitochondria. This multisubunit membrane-embedded enzyme accepts four electrons from cytochrome c and uses them to reduce 02 to 2 H20. It is also a proton pump. Its structure and functions are considered in Chapter 18. However, it is appropriate to mention here that the essential catalytic centers consist of two molecules of heme a (a and a3) and three Cu+ ions. In the fully oxidized enzyme two metal centers, one Cu2+ (of the two-copper center CuA) and one Fe3+ (heme a), can be detected by EPR spectroscopy. The other Cu2+ (CuB) and heme a3 exist as an EPR-silent exchange-coupled pair just as do the two copper ions of hemocyanin and of other type 3 binuclear copper centers. 

A number of copper -containing protein compounds are enzymes with an oxidase function (ascorbic acid oxidase, urease, etc 1 and these play an important role in Ihe biological oxidation-reduction system. There is a definite relationship of copper with iron in connection with utilization of iron in hemoglobin function. 

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