Oxidases cytochrome c oxidase

Cytochrome c oxidase. Cytochrome c oxidase is an enzyme that occurs in the inner mitochondrial membrane and, as we have seen, catalyzes the four-electron reduction of dioxygen to water as the final reaction in the... 

Nonblue oxidases Amine oxidase Diamine oxidases Galactose oxidase Cytochrome c oxidase... 

Multicopper blue oxidases are synthesized as a single polypeptide chain, which is composed of three BCB domains in the case of laccases (LC) and ascorbate oxidases (AO) and six such domains in ceruloplasmin (CP) and hephaestin (HP). Structurally they are arranged in a triangular manner. These enzymes, along with heme-copper oxidases (cytochrome c oxidases and quinol-oxidases) and a cyanide-resistant alternative oxidase found in mitochondria of plants and fungi, are the only known enzymes capable of catalyzing four-electron reduction of dioxygen to water. In the... 

The simple coordination chemistry characteristic of the majority of protein-metal interactions is replaced in certain cases by irreversible covalent modifications of the protein mediated by the metal ion. These modifications are essential for the function and are templated by the structure of the protein, as no other proteins are required for the reaction to occur. These self-processing reactions result in the biogenesis of redox cofactors in some enzymes (amine oxidases, galactose oxidase, cytochrome c oxidase) and activation of hydrolytic sites in others (nitrile hydratase). The active sites of all of these enzymes are bifunctional, directing not only the catalytic turnover reaction of the mature enzyme but the modification steps required for maturation. 

Cytochromes, as components of electron transfer chains, must interact with the other components, accepting electrons from reduced donor molecules and transferring them to appropriate acceptors. In the respiratory chain of the mitochondria, the ubiquinolxytochrome c oxidoreductase, QCR or cytochrome bc complex, transfers electrons coming from Complexes 1 and 11 to cytochrome c. The bc complex oxidises a membrane-localised ubiquinol the redox process is coupled to the translocation of protons across the membrane, in the so-called proton-motive Q cycle, which is presented in a simplified form in Figure 13.14. This cycle was first proposed by Peter Mitchell 30 years ago and substantially confirmed experimentally since then. The Q cycle in fact consists of two turnovers of QH2 (Figure 13.14). In both turnovers, the lipid-soluble ubiquinol (QH2) is oxidized in a two-step reoxidation in which the semiquinone CoQ is a stable intermediate, at the intermembrane face of the mitochondrial inner membrane. It transfers one electron to the Rieske iron—sulfur protein (ISP), one electron to one of the two cytochrome b haems (bi), while two protons are transferred to the intermembrane space. In both of the Q cycles, the cytochrome bi reduces cytochrome bfj while the Reiske iron—sulfur cluster reduces cytochrome c/. The cytochrome ci in turn reduces the water-soluble cytochrome c, which transfers its electrons to the terminal oxidase, cytochrome c oxidase, described above. In one of the two Q cycles, reduced cytochrome bf reduces Q to the semiquinone, which is then reduced to QH2 by the second reduced cytochrome bn- The protons required for this step are derived from the matrix side of the membrane. The overall outcome of the two CoQ cycles (10) (/ — matrix o — intermembrane space) is... 

Heme-copper oxidases Cytochrome c oxidase 2H 0, Proton translocaikm ... 

Cytochrome c cytochrome c oxidase cytochrome c/cytochrome c oxidase cytochrome c oxidase/CO complex Vesicle-resident cytochromes... 

Cytochrome c Oxidase. Cytochrome c oxidase catalyses the reduction of dioxygen to water and the redox active components comprise a dicopper centre... 

Many key protein ET processes have become accessible to theoretical analysis recently because of high-resolution x-ray stmctural data. These proteins include the bacterial photosynthetic reaction centre [18], nitrogenase (responsible for nitrogen fixation), and cytochrome c oxidase (the tenninal ET protein in mammals) [19, 20]. Although much is understood about ET in these molecular machines, considerable debate persists about details of the molecular transfonnations. 

Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawaitoh K, Nakashima R, Yaono R and Yoshikawa S 1995 Structures of metai sites of oxidized bovine heart cytochrome c oxidase at 2.8 angstrom Science 269 1069-74... 

Hofacker, I., Schulten, K. Oxygen and proton pathways in cytochrome-c oxidase. Proteins Str. Funct. Genet. 29 (1998) 100-107... 

Cytochrome c oxidase (from bovine heart mitochondria). [9001-16-5] Mr 100,0007haeme,... 

Despite considerable efforts very few membrane proteins have yielded crystals that diffract x-rays to high resolution. In fact, only about a dozen such proteins are currently known, among which are porins (which are outer membrane proteins from bacteria), the enzymes cytochrome c oxidase and prostaglandin synthase, and the light-harvesting complexes and photosynthetic reaction centers involved in photosynthesis. In contrast, many other membrane proteins have yielded small crystals that diffract poorly, or not at all, using conventional x-ray sources. However, using the most advanced synchrotron sources (see Chapter 18) it is now possible to determine x-ray structures from protein crystals as small as 20 pm wide which will permit more membrane protein structures to be elucidated. 

Iwata, S., Ostermeier, C., Ludwig, B., Michel, H. Structure at 2.8 A resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376 660-669, 1995. 

Tsukihara, T., et al. The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A resolution. Science 272 1136-1144, 1996. 

Mammalian sulfite oxidase is the last enzyme in the pathway for degradation of sulfur-containing amino acids. Sulfite oxidase (SO) catalyzes the oxidation of sulfite (SO ) to sulfate (S04 ), using the heme-containing protein, cytochrome c, as electron acceptor ... 

Complex IV Cytochrome c Oxidase The Thermodynamic View of Chemiosmotic Coupling ATP Synthase... 

Why has nature chosen this rather convoluted path for electrons in Complex 111 First of all. Complex 111 takes up two protons on the matrix side of the inner membrane and releases four protons on the cytoplasmic side for each pair of electrons that passes through the Q cycle. The apparent imbalance of two protons in ior four protons out is offset by proton translocations in Complex rV, the cytochrome oxidase complex. The other significant feature of this mechanism is that it offers a convenient way for a two-electron carrier, UQHg, to interact with the bj and bfj hemes, the Rieske protein Fe-S cluster, and cytochrome C, all of which are one-electron carriers. 

Cytochrome c, like UQ is a mobile electron carrier. It associates loosely with the inner mitochondrial membrane (in the intermembrane space on the cytosolic side of the inner membrane) to acquire electrons from the Fe-S-cyt C aggregate of Complex 111, and then it migrates along the membrane surface in the reduced state, carrying electrons to cytochrome c oxidase, the fourth complex of the electron transport chain. 

Complex rV is called, cytochrome c oxidase because it accepts electrons from cytochrome c and directs them to the four-electron reduction of O2 to form H2O ... 

FIGURE 21.14 All electrophoresis gel showing the complex subunit structure of bovine heart cytochrome c oxidase. The three largest subunits, I, II, and III, are coded for by mitochondrial DNA. The others are encoded by unclear DNA. (Photo kindly provided by Professor Roderick Capaldi)... 

Thus, Og and cytochrome c oxidase are the final destination for the electrons derived from the oxidation of food materials. In concert with this process, cytochrome c oxidase also drives transport of protons across the inner mitochondrial membrane. These important functions are carried out by a transmembrane protein complex consisting of more than 10 subunits (Table 21.2). 

FIGURE 21.17 The electron transfer pathway for cytochrome oxidase. Cytochrome c binds on the cytosolic side, transferring electrons through the copper and heme centers to reduce O9 on the matrix side of the membrane. 

Cytochrome c oxidase contains two heme centers (cytochromes a and %) as well as two copper atoms (Figure 21.17). The copper sites, Cu and Cug, are associated with cytochromes a and respectively. The copper sites participate in electron transfer by cycling between the reduced (cuprous) Cu state and the oxidized (cupric) Cu state. (Remember, the cytochromes and copper sites are one-electron transfer agents.) Reduction of one oxygen molecule requires passage of four electrons through these carriers—one at a time (Figure... 

The link with the final electron acceptor, O2, is the enzyme cytochrome c oxidase which spans the inner membrane of the mitochondrion. It consists of cytochromes a and a3 along with two, or possibly three, Cu atoms. The details of its action are not fully established but the overall reaction catalysed by the enzyme is ... 

Cytochrome c oxidase contains two, or possibly three, copper atoms referred to as Cua and Cub since they do not fit into the usual classification. The former (possibly a dimer) is situated outside the mitochondrial membrane, whereas the latter is associated with an iron atom within the membrane. Both have electron transfer functions but details are as yet unclear. 

Chemical structure and reaction mechanisms of cytochrome c oxidase. R. Lemberg, Rev. Pure Appl. Chem., 1965,15,125-136 (132). 

Cytochrome enzymes, 2, 772 Cytochrome a3 oxidase, 6, 697 Cytochrome c oxidase, 6, 683 copper complexes, 2,724,772 Cytochrome oxidases, 6, 624 bacterial, 6,696... 

Figure 8. Mechanism of cytochrome c oxidase. Explanation given in text.

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

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