Cytochrome c oxidase I

Minnaert, K., 1961, The kinetics of cytochrome c oxidase I. The system cytochrome c-cytochrome oxidase-oxygen, Biochim. Biophys. Acta. 50 23934. 

Steffens, G., and Buse, G., 1976, Studies on Cytochrome c oxidase, I Purification and characterization of the enzyme from bovine heart and identification of peptide chains in the complex, Hoppe-Seyleris Z. Physiol. Chem. 357 1125nll37. 

For every four electrons transferred from reduced cytochrome c through cytochrome c oxidase (i.e., for every molecule of O2 reduced to two H2O molecules), four protons are translocated from the matrix space to the intermembrane space (two protons per electron pair). However, the mechanism by which these protons are translocated is not known. 

Berendonk, T.U. (2006). Intraspecific genetic variation in Paramecium revealed by mitochondrial cytochrome c oxidase I sequences. Journal of Eukaryotic Microbiology 53, 20-25. 

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

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)... 

Section 18.2). The latest generation of such catalysts (1 in Fig. 18.17) reproduces the key features of the site (i) the proximal imidazole ligation of the heme (ii) the trisi-midazole ligation of distal Cu (iii) the Fe-Cu separation and (iv) the distal phenol covalently attached to one of the imidazoles. As a result, binding of O2 to compound 1 in its reduced (Fe Cu ) state appears to result in rapid reduction of O2 to the level of oxides (—2 oxidation state) without the need for outer-sphere electron transfer steps [Collman et ah, 2007b]. This reactivity is analogous to that of the heme/Cu site of cytochrome c oxidase (see Section 18.2). 

Biomimetic studies typically have one or more of the following objectives (i) to reproduce in a small synthetic molecule reactivity that was theretofore only observed in an enzyme (ii) to understand the mechanisms of an enzymatic reaction and the relationship between the stereoelectronic attributes of the catalytic site and its reactivity and (iii) to develop practical catalysts by exploiting and adopting solutions that evolved in Nature. Biomimetic studies of cytochrome c oxidase have been particularly impactfull in addressing aim (ii). On the other hand, this approach is... 

Collman JP, Sunderland CJ, Berg KE, Vance MA, Solomon El. 2003c. Spectroscopic evidence for a heme-superoxide/Cu(I) intermediate in a functional model of cytochrome c oxidase. J Am Chem Soc 125 6648. 

Belevich I, Verkhovsky MI, Wikstrom M (2006) Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase. Nature 440 829-832. 

Okamoto, M., Bessho, Y., Kamiya, M., Kurosawa, T. and Horii, T. (1995) Phylogenetic relationships within Taenia taeniaeformis varian Is and other taeniid cestodes inferred from the nucleotide sequence of the cytochrome c oxidase subunit I gene. Parasitology Research 81, 451-458. 

Mitochondrial DNA is inherited maternally. What makes mitochondrial diseases particularly interesting from a genetic point of view is that the mitochondrion has its own DNA (mtDNA) and its own transcription and translation processes. The mtDNA encodes only 13 polypeptides nuclear DNA (nDNA) controls the synthesis of 90-95% of all mitochondrial proteins. All known mito-chondrially encoded polypeptides are located in the inner mitochondrial membrane as subunits of the respiratory chain complexes (Fig. 42-3), including seven subunits of complex I the apoprotein of cytochrome b the three larger subunits of cytochrome c oxidase, also termed complex IV and two subunits of ATPase, also termed complex V. 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

Cytochrome c oxidase is an enzyme that couples the one-electron oxidation of cytochrome c to the four-electron reduction of 02 and is thus a crucial component of respiration. Cytochrome c contains the redox-active heme c, while cytochrome c oxidase contains a dinuclear Cua redox site in subunit II and three redox-active sites in subunit I heme a, heme a3, and Cur. It is believed that heme a is an electron-transfer site, while heme a3 and Cur function together at the 02 reduction site. 

The realization of the widespread occurrence of amino acid radicals in enzyme catalysis is recent and has been documented in several reviews (52-61). Among the catalytically essential redox-active amino acids glycyl [e.g., anaerobic class III ribonucleotide reductase (62) and pyruvate formate lyase (63-65)], tryptophanyl [e.g., cytochrome peroxidase (66-68)], cysteinyl [class I and II ribonucleotide reductase (60)], tyrosyl [e.g., class I ribonucleotide reductase (69-71), photosystem II (72, 73), prostaglandin H synthase (74-78)], and modified tyrosyl [e.g., cytochrome c oxidase (79, 80), galactose oxidase (81), glyoxal oxidase (82)] are the most prevalent. The redox potentials of these protein residues are well within the realm of those achievable by biological oxidants. These redox enzymes have emerged as a distinct class of proteins of considerable interest and research activity. 

The authors also examined a model which describes the paramagnetic site in terms of a Cu(I) ion coordinated to a sulfur n radical213,214). In the discussion of the magnetic data, however, they show that the proton hf parameters and the g tensor found for cytochrome c oxidase are not consistent with a thiyl radical ligated to a Cu(I) center. 

Copper, Cu (d °), Cu " (d ) 4, tetrahedral Y-Thiolate, thioether, A-imidazoIe Electron transfer in Type I bine copper proteins and Type III heme-copper oxidases (Cua in cytochrome c oxidase, for example)... 

Cytochrome c and ubiquinol oxidases are part of an enzyme superfamily coupling oxidation of ferrocytochrome c (in eukaryotes) and ubiquinol (in prokaryotes) to the 4 e /4 reduction of molecular oxygen to H2O. After this introduction, we will concentrate on the cytochrome c oxidase enzyme. The two enzymes, cytochrome c oxidase (CcO) and ubiquinol oxidase, are usually defined by two criteria (1) The largest protein subunit (subunit I) possesses a high degree of primary sequence similarity across many species (2) members possess a unique bimetallic center composed of a high-spin Fe(II)/(III) heme in close proximity to a copper ion. Cytochrome c oxidase (CcO) is the terminal... 

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