Hemocyanin cytochrome oxidases

Copper has an essential role in a number of enzymes, notably those involved in the catalysis of electron transfer and in the transport of dioxygen and the catalysis of its reactions. The latter topic is discussed in Section 62.1.12. Hemocyanin, the copper-containing dioxygen carrier, is considered in Section 62.1.12.3.8, while the important role of copper in oxidases is exemplified in cytochrome oxidase, the terminal member of the mitochondrial electron-transfer chain (62.1.12.4), the multicopper blue oxidases such as laccase, ascorbate oxidase and ceruloplasmin (62.1.12.6) and the non-blue oxidases (62.12.7). Copper is also involved in the Cu/Zn-superoxide dismutases (62.1.12.8.1) and a number of hydroxylases, such as tyrosinase (62.1.12.11.2) and dopamine-jS-hydroxylase (62.1.12.11.3). Tyrosinase and hemocyanin have similar binuclear copper centres. 

The type 3 centre is present in the blue oxidases, and in hemocyanin, tyrosine and dopamine /3-hydroxylase. Cytochrome oxidase, like laccase, contains four metal centres including an antifer-romagnetically linked Fe- -Cu pair. It appears that there are considerable similarities between the type 3 site and the cytochrome a3- -CuB site in cytochrome oxidase. 

In the following sections, examples of all the classes of reaction given above will be discussed, with emphasis on those that have been well studied. Many of the enzymes involved in these processes are hemoproteins, but non-heme prosthetic groups are important in oxygenases and are also present in some oxidases. Copper is an important metal in this context, and is present in the oxygen transport protein hemocyanin, and in oxidases such as cytochrome oxidase and laccase. Some flavoenzymes are important too, but will not be covered in this discussion. 

The clinical symptoms of classical Menkes disease can be traced back to developmentaUy important copper enzymes such as lysyl oxidase, tyrosinase (see Copper Hemocyanin/Tyrosinase Models), cytochrome c oxidase (see Cytochrome Oxidase), dopamine -hydroxylase, superoxide dismutase, and amine oxidase (see Superoxide Dismutase). Lysyl oxidase is needed for the cross-linking of connective tissue a deficiency in this enzyme causes weakened connective tissue and connective tissue disorder such as arterial ruptures as observed in these patients. Low levels of cytochrome c oxidase cause temperature instability and the absence of tyrosinase explains the hair depigmentation observed in affected individuals. ... 

Copper Hemocyanin/Tyrosinase Models Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 1 Sites Copper Proteins with Type 2 Sites Cytochrome Oxidase Electron Transfer Reactions Theory Long-range Electron Transfer in Biology Metal Ion Toxicity Metal-related Diseases of Genetic Origin Metallochaperones Metal Ion Homeostasis Nutritional Aspects of Metals Trace Elements. 

Heme derivatives. Name for derivatives of heme, i.e., for iron complexes of the porphyrins and hy-droporphyrins, in the strictest sense of protoporphy-rins. These H. d. are the prosthetic groups of hemo-proteins such as the cytochromes, cytochrome oxidase, peroxidases, catalases, leghemoglobin, nitrite reductases, sulfite reductase see also heme d, heme di, and siroheme. In spite of their similar names heme-rythrin, hemocyanin, hemocuprein, and hemovana-dins do not belong to the H. d. 

In certain copper-containing proteins the copper appears to serve principally in electron transport with no evidence of CU-O2 interaction, such as in cytochrome oxidase. Of importance, however, is that many copper proteins and enzymes participate in reactions in which the oxygen molecule is directly or indirectly involved. An example is hemocyanin, the oxygen carrier in the blood of certain sea animals such as snails, octopus, and Crustacea. Oxygenated hemocyanin is blue and the cephalopods (crabs and lobsters) are literally the blue bloods of the animal kingdom. Hemocyanins are giant molecules of MW > 10 that occur free in solution. 

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. 

Figure 5.1 Schematic representations of selected active sites of the copper proteins plastocyanin [56] (type 1, a) galactose oxidase [57] (type 2, b) oxy hemocyanin [58] (type 3, c) ascorbate oxidase [10] (type 4, or multicopper site, d) nitrous oxide reductase [59] (CuA site, e) cytochrome c oxidase [15]...

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