Oxidoreductases copper oxidases

Laccases (p-diphenol O2 oxidoreductase EC 1.10.3.2) catalyze the oxidation of p-diphenols with the concurrent reduction of dioxygen to water. However, the actual substrate specificities of laccases are often quite broad and vary with the source of the enzyme [116,117]. Laccases are members of the blue copper oxidase enzyme family. Members of this family have four cupric (Cu +) ions where each of the known magnetic species (type 1, type 2, and type 3) is associated with a single polypeptide chain. In the blue copper oxidases the Cu + domain is highly conserved and, for some time, the crystallographic structure of ascorbate oxidase, another member of this class of enzymes, has provided a good model for the structure of the laccase active site [124,125]. The crystal structure of the Type-2 Cu depleted laccase from Coprinus cinereus at 2.2. A resolution has also been elucidated [126]. 

Blue copper oxidase (BCO) is a classification of oxidoreductase enzymes that contain at least one blue or T1 copper and a T2AT3 trinuclear cluster. These enzymes typically give rise to a characteristic blue color as a result of a strong absorption band around... 

Polyphenol oxidase (PPO) (EC 1.14.18.1 monophenol monooxygenase [tyrosinase] or EC 1.10.3.2 0-diphenol 02-oxidoreductase) is one of the more important enzymes involved in the formation of black tea polyphenols. The enzyme is a metallo-protein thought to contain a binudear copper active site. The substance PPO is an oligomeric particulate protein thought to be bound to the plant membranes. The bound form of the enzyme is latent and activation is likely to be dependent upon solubilization of the protein (35). PPO is distributed throughout the plant (35) and is localized within in the mitochondria (36), the cholorplasts (37), and the peroxisomes (38). Using antibody techniques, polyphenol oxidase activity has also been localized in the epidermis palisade cells (39). Reviews on the subject of PPO are available (40—42). 

These complexes are usually named as follows I, NADH-ubiquinone oxidoreductase II, succinate-ubiquinone oxidoreductase III, ubiquinol-cytochrome c oxidoreductase IV, cytochrome c oxidase. The designation complex V is sometimes applied to ATP synthase (Fig. 18-14). Chemical analysis of the electron transport complexes verified the probable location of some components in the intact chain. For example, a high iron content was found in both complexes I and II and copper in complex IV. 

Complex IV. Cytochrome c oxidase (ubiquinol-cytochrome c oxidoreductase). Complex IV from mammalian mitochondria contains 13 subunits. All of them have been sequenced, and the three-dimensional structure of the complete complex is known (Fig. 18-10).125-127 The simpler cytochrome c oxidase from Paracoccus denitrificans is similar but consists of only three subunits. These are homologous in sequence to those of the large subunits I, II, and III of the mitochondrial complex. The three-dimensional structure of the Paracoccus complex is also known. Its basic structure is nearly identical to that of the catalytic core of subunits I, II, and III of the mitochondrial complex (Fig. 18-10,A).128 All three subunits have transmembrane helices. Subunit III seems to be structural in function, while subunits I and II contain the oxidoreductase centers two hemes a (a and a3) and two different copper centers, CuA (which contains two Cu2+) and a third Cu2+ (CuB) which exists in an EPR-silent exchange coupled pair with a3. Bound Mg2+ and Zn2+ are also present in the locations indicated in Fig. 18-10. 

The electron carriers in the respiratory assembly of the inner mitochondrial membrane are quinones, flavins, iron-sulfur complexes, heme groups of cytochromes, and copper ions. Electrons from NADH are transferred to the FMN prosthetic group of NADH-Q oxidoreductase (Complex I), the first of four complexes. This oxidoreductase also contains Fe-S centers. The electrons emerge in QH2, the reduced form of ubiquinone (Q). The citric acid cycle enzyme succinate dehydrogenase is a component of the succinate-Q reductase complex (Complex II), which donates electrons from FADH2 to Q to form QH2.This highly mobile hydrophobic carrier transfers its electrons to Q-cytochrome c oxidoreductase (Complex III), a complex that contains cytochromes h and c j and an Fe-S center. This complex reduces cytochrome c, a water-soluble peripheral membrane protein. Cytochrome c, like Q, is a mobile carrier of electrons, which it then transfers to cytochrome c oxidase (Complex IV). This complex contains cytochromes a and a 3 and three copper ions. A heme iron ion and a copper ion in this oxidase transfer electrons to O2, the ultimate acceptor, to form H2O. 

This topic has been reviewed by Ingledew (55). The major components of the respiratory chain for T. ferrooxidans are a cytochrome oxidase of the Ci type, cytochromes c, and the blue copper protein rusticyanin. Initial electron transfer from Fe(II) to a cellular component takes place at the outer surface of the plasma membrane in the periplasmic space. The rate of electron transfer from Fe(II) to rusticyanin is too slow for rusticyanin to serve as the initial electron acceptor. Several proposals have been made for the primary site of iron oxidation. Ingledew (56) has suggested that the Fe(II) is oxidized by Fe(III) boimd to the cell wall the electron then moves rapidly through the polynuclear Fe(III) complex to rusticyanin or an alternative electron acceptor. Other proposals for the initial electron acceptor include a three-iron-sulfur cluster present in a membrane-bound Fe(II) oxidoreductase (39, 88), a 63,000 molecular weight Fe(II)-oxidizing enzyme isolated from T. ferrooxidans (40), and an acid-stable cytochrome c present in crude extracts of T. ferrooxidans (14). 

Cytochrome oxidase (cytochrome c 02 oxidoreductase, EC 1.9.3.1) is the terminal enzyme in the mitochrondial electron transport chain. It contains two heme irons and two coppers in the functional unit and is the subject of intensive current study, in part because of the significance of its three functions. It carries out the reduction of dioxygen to water with the oxidation of ferrocytochrome c and somehow allows for the production of ATP. The study of each one of these three processes are enormous tasks still in their relatively early stages, but there is sufficient evidence that multimetal centers play a role, at least in the reduction of dioxygen, to justify inclusion in this review. 

Other oxidoreductases that can play a major or less important role in drug metabolism are hemoglobin, monoamine oxidases (EC 1.4.3.4 MAO-A and MAO-B), which are essentially mitochondrial enzymes, the cytosolic molybdenum hydroxylases (xanthine oxidase, EC 1.1.3.22 xanthine dehydrogenase, EC 1.1.1.204 and aldehyde oxidase, EC 1.2.3.1), d the broad group of copper-containing amine oxidases (EC 1.4.3.6) (36-39). 

Copper amine oxidases (EC 1.4.3.6) [CAOs, amine O2 oxidoreductase (deaminating)] catalyze the oxidative deamination of biogenic amines to corresponding aldehydes and ammonia, accompanied by a two-electron reduction of molecular oxygen to hydrogen peroxide [7] ... 

Polymer Modification by Oxidoreductases. Tyrosinase (polyphenol oxidase, a copper-containing monooxygenation enzyme) was used as catalyst for modification of chitosan. The enzymatic treatment of chitosan film in the presence of tyrosinase and phenol derivatives produced a new material of chitosan derivative (309). During the reaction, imstable o-quinones were formed, followed by the reaction with chitosan to give the modified chitosan. In the enzymatic treatment of p-cresol with a low concentration of chitosan (<1%), the reaction solution was converted into a gel (310). 

Besides the large group of hydrolytic enzymes, metal ions are often present in enzymes, which catalyze redox processes. Nature provides a large number of oxidoreductases, which catalyze diverse reactions. Many of them are copper enzymes that use O2 as the ultimate oxidant. A prominent example for such a type-2 copper enzyme is galactose oxidase. The structure of galactose oxidase and its mechanism... 

Copper is an essential trace element for humans and other animals. Copper ions are included in the active centres of many enzymes, especially cytochrome c oxidase, superoxide dismutase, various aminoxidases (such as lysyl oxidase), hydroxylases (e.g. dopamine -hydroxylase and tyrosinase), galactose oxidase or different phenoloxidases, such as laccase and other oxidoreductases. The so-called blue copper proteins, for example plastocyanin, azurin and plantacyanin, occur in many prokaryotic organisms and plants. These proteins, by a change to the bound copper valency, provide electron transfer in various redox processes. 

Electroactive polyaniline films were synthesized by the catalysis of biUru-bin oxidase (BOD, a copper-containing oxidoreductase). The polymerization of aniline was carried out on the surface of a sohd matrix such as glass sUde, plastic plate, or platinum electrode to form homogeneous films [33]. The BOD was immobilized on the surface by physical absorption. The optimum pH was around 5.5. Some aniline derivatives such as p-aminophenol and p-phenylenediamine were good substrates for BOD. Structural analysis suggested the BOD synthesized polyanihne possessed partially 1,2-substititued structures. Cyclic voltammetric studies demonstrated that the PANl films were electrochemically reversible in redox properties, but differed from that of chemically or electrochemically synthesized PANl. The difference was attributed to the partial 1,2-substitution. Laccases are known to oxidize phenolic compounds in nature in the presence of oxygen and are capable in polyaniline synthesis in vitro [34-36]. 

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