Enzymes copper and

Figure 1.1 Some redox potentials (in volts) of iron and copper enzymes and chelates at pH 7 relative to the standard hydrogen electrode. From Crichton and Pierre, 2001. Reproduced by permission of Kluwer academic publishers.

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... 

Kopf, M.-A. Karlin, K. D. Models of copper enzymes and heme-copper oxidases, Biomimetic Oxidations Catalyzed by Transition Metal Complexes , Ed. Meunier, B. Imperial College Press London, 2000, pp. 309—362. 

Table 1. Reduction of dioxygen by copper enzymes and their substrates (and cosubstrates)...

Recently, Cottam and Ward (182) found that with the titration of apo-alkaline phosphatase with Zn(II) up to a mole ratio of four Zn(II/ dimer results in no increase in the S5C1 NMR linewidth, .. . while in previous studies of zinc activated biological reactions, a large increase in the chloride linewidth was observed with zinc bound to macromolecules. However, an increase in the chloride linewidth is observed when the pH is decreased below 5.0. This was interpreted as showing that Zn(II) in alkaline phosphatase is not exposed to solvent at pH > 5.0. In an ESR study of Cu(II) binding to alkaline phosphatase, Csopak and Falk (133) reported that two Cu(II) binds to the same specific sites as the two Zn(II), that the ESR spectrum for the one copper enzyme is different from the two copper enzymes, and that phosphate binding causes a shift of the spectral lines. 

Most copper enzymes and proteins are found only in eukaryotes, but a few copper proteins, such as azurin and plastocyanin are also present in certain prokaryots... 

Hydroxylation of tyrosine to L-dopa in the pigment cells involves tyrosinase, a copper enzyme and requires no tetrahydrobiopterin. 

Laccase was discovered in 1883 by Yoshida (4), who found that the latex of the Chinese or Japanese lacquer tree rapidly hardened to a plastic in the presence of oxygen, and he attributed this to the presence of a diastase in the lacquer. A few years later Bertrand (5) further purified this enzyme and named it laccase. He suggested that laccase is a metalloprotein containing manganese and introduced the term oxidase. About 50 years later Keilin and Mann (6) demonstrated that laccase is a copper enzyme and showed that its blue color disappears reversibly upon addition of substrate. Laccase has been extensively reviewed by the researchers in this field over the last 20 years, and a representative selection is listed (3, 7-12). 

Lastly the copper oxidases that appear in mammals are listed. Many of these seem similar to their counterparts in the plant kingdom with the exception of some forms of superoxide dismutase. In mammals it is a zinc-copper enzyme and catalyzes the dismutation of the 02" radical according to the reaction Oj" + O2" + 2H" — H2O2 + O2. This reaction... 

The terminal component of the respiratory chain is cytochrome c oxidase, which reduces dioxygen to two molecules of water. This cytochrome was discovered as the Atmungsferment by Warburg already in the 1920s and shown by him to be a heme protein in 1929 [2], an achievement for which he was awarded the Nobel Prize for Physiology or Medicine in 1931. The electron donor of the oxidase, cytochrome c, had been found earlier by Keilin (see [3]), as had one of the oxidase heme components, cytochrome a, whereas Keilin did not observe the dioxygen-reacting cytochrome fl3 until 1939. Keilin had before this discovery maintained that the oxidase is not a heme but a copper enzyme, and we now know that it also contains two... 

Copper is necessary, together with iron, for hematopoiesis, probably partly because it is needed for the synthesis of fer-roxidase (ceruloplasmin). Many enzymes require copper for activity. Examples of some of the copper-enzymes and their functions are given in Table 37-5. Mitochondrial iron uptake may be blocked by deficiency of a cuproprotein, perhaps cytochrome oxidase. Several inherited diseases involving abnormalities in copper metabolism (Wilson s disease, Menkes syndrome) or copper enzymes (X-linked cutis laxa, albinism) occur in human and in several animal species. 

All of the currently known copper proteins which contain type 1 copper centers are derived from a common ancestor. The various characteristics of the small blue proteins, and the development from copper proteins to copper enzymes and from there to non-catalytic, non-copper proteins are the results of a solely divergent evolution. 

We have mentioned earlier the dissimilarities between the spectral properties of chromophoric metal ions at the active sites of metalloen-zymes and the properties of simple bidentate model complexes of the same metals. Cobalt phosphatase has served well to illustrate such a dissimilarity and, in Figure 9, the data for phosphatase, representative of a cobalt enzyme, are shown again along with those for plastocyanin, a copper enzyme, and ferredoxin, an iron enzyme. Each enzyme spectrum is unusual compared with the simple model complexes shown at the bottom of the figure. More detailed spectral data as well as comparison of other physical properties of metalloenzymes—e.g., electron paramagnetic resonance spectra—with those of model complexes have been summarized previously (10). 

Various nuclearities are found in redox copper enzymes and their activity relates to the structure of their active site (Figure 2). Type 1 sites have a saturated coordination sphere and are dedicated to pure electron transfer. Type 2 sites ( normal copper, named after their normal d-d visible transition) are mononuclear, display a labile site for O2 coordination and activation, the rest of the coordination sphere being of type N3, N2S, or N2O2. In hydroxylases, PHM, Dj6H, and T 6H (tyramine )8-monooxygenase), the Cu/02 adduct, a superoxide Cu(II) complex, carries out... 

---