Cytochrome c oxidase reactions

Figure 7.40 The cytochrome c oxidase reaction cycle starting from the mixed-valence state.

The cytochrome c oxidase reaction under initial steady state conditions is as follows ... 

It is important to recognize that a complete initial steady state kinetic analysis of the cytochrome c oxidase reaction has yet to be undertaken. The complete set of enzyme reactants includes four ferrocytochrome c molecules and one O2 molecule as substrates, and because of the extremely low... 

The cytochrome c oxidase reaction encompasses the so-called third site of oxidative phosphorylation. There is no doubt that oxidation of cytochrome c by dioxygen results in generation of pmf. Cytochrome oxidase was long believed to do so simply by catalysing transmembranous electron transfer, with uptake of the protons required in reduction of Oj to water from the M phase. Such a function is thermodynamically equivalent to translocation of one proton per transferred electron, although no protons appear on the C side [8]. 

Giuffre A, Barone MC et al (2000) Reactirai of nitric oxide with the turnover intermediates of cytochrome C oxidase reaction pathway and fimctiraial effects. Biochemistry 39 15446-15453... 

Poly-L-lysine inhibits the electrode reaction of native horse heart cytochrome c, as shown by dc voltammetry (Figure 3), again analogous to its inhibiting effect on the cytochrome c-oxidase reaction. The effect on the ac cyclic voltammetry peak current, //,(ac), is more marked. The varation with poly-L-lysine concentration is consistent with adsorption of poly-L-lysine onto the electrode surface, decreasing the effective free electrode area. 

Spectral examination of the reaction of reduced cytochrome c oxidase with molecular oxygen has shown the formation of at least three intermediates, designated as Compounds I, II, and III according to the order of their appearance, observed at — 80°C in intact mitochondria (Chance et al, 1975a,b). Compound I is thought to be an active intermediate in the true oxygenated compound in the cytochrome c oxidase reaction sequence. The decay of Compound I is accelerated by some 2 x 10" times in the presence of ferrocytochrome c. Present data suggest that ferrocytochrome c may transfer electrons to cytochrome oxidase in two steps, namely the reduction... 

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. 

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. 

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 ... 

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

Figure 18.2 Summary of respiratory energy flows. Foods ate converted into the reduced form of nicotinamide adenine dinucleotide (NADH), a strong reductant, which is the most reducing of the respiratory electron carriers (donors). Respiration can he based on a variety of terminal oxidants, such as O2, nitrate, or fumarate. Of those, O2 is the strongest, so that aerobic respiration extracts the largest amount of free energy from a given amount of food. In aerobic respiration, NADH is not oxidized directly by O2 rather, the reaction proceeds through intermediate electron carriers, such as the quinone/quinol couple and cytochrome c. The most efficient respiratory pathway is based on oxidation of ferrocytochrome c (Fe ) with O2 catalyzed by cytochrome c oxidase (CcO). Of the 550 mV difference between the standard potentials of c)Tochrome c and O2, CcO converts 450 mV into proton-motive force (see the text for further details).

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, Decreau RA, Yan Y, Yoon J, Solomon El. 2007a. Intramolecular single-turnover reaction in a cytochrome c oxidase model bearing a Tyr244 mimic. J Am Chem Soc 129 5794. 

Wever R, Van Gelder BF, Der Vartanian DV. 1975. Biochemical and biophysical studies on cytochrome c oxidase XX. Reaction with sulphide. Biochem Biophys Acta 387 189-193. 

Cytochrome c is responsible for accepting an electron from cytochrome Ci and transferring it to cytochrome c oxidase. The electron transfer reaction may occur via the exposed portion of the ring or by tunnelling through the protein (and involving an outer-sphere mechanism). The details of this process have not been fully elucidated and have remained the focus of much research. 

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... 

Sulfite oxidase is a dimetallic enzyme that mediates the two-electron oxidation of sulfite by the one-electron reduction of cytochrome c. This reaction is physiologically essential as the terminal step in oxidative degradation of sulfur compounds. The enzyme contains a heme cofactor in the 10 kDa N-terminal domain and a molybdenum center in the 42 kDa C-terminal domain. The catalytic cycle is depicted in Fig. 9. 

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