Cytochrome c electron transfer

Gray HB, Winkler JR (1996) Electron transfer in proteins. Annu Rev Biochem 65 537 Fedurco M (2000) Redox reactions of heme-containing metalloproteins dynamic effects of self-assembled monolayers on thermodynamics and kinetics of cytochrome c electron-transfer reactions. Coord Chem Rev 209 263... 

In presence of TNS, reduction of cytochrome c occurs in the range of minutes instead of seconds, as it is the case for the reduction with flavocytochrome b2 or isolated cytochrome b2 core. Thus, the relative distance and orientation of the FMN, TNS and heme planes induces an electron transfer pathway different from that known for the cytochrome b2 - cytochrome c electron transfer. This clearly shows the importance of cytochrome b2 core in the electron transfer to cytochrome c. 

A). The rapidity of cytochrome c electron transfer may partly be attriliuted to the lack of substantial nuclear motion upon redox (c/. Franck-Condon principle) together with the fast low-spin Fe " to low-spin Fe" reduction rate. 

Pappa, H. S. Tajbaksh, S. Saunders, A. J. Pielak, G. J. Poulos, T. L., Probing the cytochrome c peroxidase-cytochrome c electron transfer reaction using site specific cross-ttnking. Biochemistry 1996, 35,4837-4845. 

T.L. Poulos and J. Kraut, A hypothetical model of the cytochrome c peroxidase.cytochrome c electron transfer complex, J. Biol. Chem. 255 10322 (1980),... 

It is apparent that the cytochrome c electron transfer reaction at mercury electrodes is complex and dependent on a number of parameters. The adsorption of cytochrome c at mercury is in and of itself a complicated process. The formation of the first monolayer is rapid and chemically irreversible. 

In a recent report, it was demonstrated that adsorption of 4,4 -bipyridine on platinum led to quasi-reversible rates of electron transfer with cytochrome c as evidenced by cyclic voltammetry. However, the concentration of 4,4 -bipyridine required to produce this electrochemical response was five times that which is required at gold electrodes. This difference was ascribed to the difference in the tendency of 4,4 -bipyridine to adsorb at gold and platinum electrodes. These results indicate that the use of 4,4 -bipyridine may be applicable to other solid electrodes as well for the study of cytochrome c electron transfer reactions. 

Electrons from cytochrome c are transferred to Cu sites and then passed to the heme iron of cytochrome a. Cu is liganded by two cysteines and two histidines (Figure 21.18). The heme of cytochrome a is liganded by imidazole rings of histidine residues (Figure 21.18). The Cu and the Fe of cytochrome a are within 1.5 nm of each other. 

Complex III (CoQ cytochrome c oxidoreductase) transfers electrons from CoQ to cytochrome c, through a sequence of cytochrome and iron-sulfur cofactors. Here, Alf for the couple CoQ/cytochrome c is 0.19 V, corresponding to a AG° of —36.7 kJ/mol, again enough to power the synthesis of an ATP molecule and to ensure that protons are pumped across the inner mitochondrial membrane. 

Cytochromes are electron-transfer proteins having one or several haem groups. Cytochrome c binds to the protein by one or, more commonly two, thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. Cytochrome c has been proved to be a useful model system for studying the relationship between protein structure and thermostability due to the availability of its three-dimensional structure from a wide variety of organisms, both mesophiles and thermophiles. 

The enzyme cytochrome c oxidase ( COX, EC 1.93.1) catalyzes the final step of the respiratory chain. It receives electrons from the small heme protein cytochrome c and transfers them to molecular oxygen, which is thereby reduced to water (see p. 140). At the same time, 2-4 protons per water molecule formed are pumped from the matrix into the intermembrane space. 

Various aspects of cytochrome c have been reviewed.637 648 6 1 Cytochrome c is widely distributed, and has the apparently simple role of accepting an electron from cytochrome c, and transferring it to cytochrome oxidase. A major area of discussion is the pathway taken by the electron in its route from the surface of (he protein to the heme and out again. 

Step 3 Complex IV. The cytochrome oxidase complex consists of at least 13 polypeptides and functions as a dimer. It accepts electrons form cytochrome c and transfers them to the final acceptor oxygen. From two molecules of reduced cytochrome c, this reaction pumps two protons (one proton/electron) to the intermembrane space. 

Coenzyme Q passes electrons through iron-sulfur complexes to cytochromes b and ch which transfer the electrons to cytochrome c. In the ferric Fe3+ state, the heme iron can accept one electron and be reduced to the ferrous state Fe2+. Since the cytochromes carry one electron at a time, two molecules on each cytochrome complex are reduced for every molecule of NADH that is oxidized. The electron transfer from coenzyme Q to cytochrome c produces energy, which pumps protons across the inner mitochondrial membrane. The proton gradient produces one ATP for every coenzyme Q-hydrogen that transfers two electrons to cytochrome c. Electrons from FADH2, produced by reactions such as the oxidation of succinate to fumarate, enter the electron transfer chain at the coenzyme Q level. 

In the catalytic cycle in Scheme 1, details of the reaction between the high-valent iron-oxo porphyrin n radical cation [(P)Fe =0] + and a substrate have yet to be clarified [66]. Three possibilities have survived after extensive studies of the mechanisms of the reactions of high-valent iron-oxo porphyrins, in particular the dealkylation of amines by cytochrome P-450 (A) a sequential electron-proton electron transfer (B) direct hydrogen transfer then electron transfer and (C) electron transfer followed by hydrogen transfer (Scheme 2) [67-74]. 

Complex 111 transfers electrons from the quinone pool dissolved in the membrane to the pool of cytochrome c loosely associated with the cytosolic face of the membrane. This complex also operates with a near equilibrium between AjaH+ and the oxido-reduction span of the electrons. In contrast the final complex of the mitochondrial respiratory chain, cytochrome c oxidase, transferring electrons from cytochrome c to oxygen, operates under non-equilibrium conditions and is strictly irreversible. 

Electrons from cytochrome c are transferred rapidly (k = 8xl0 M -s ) to haem a and Cu - Although the former has been suggested to be the primary electron acceptor, this view is presently uncertain due to the very fast electron equilibration between the two receiving centres [127,128],... 

Two cytochromes have been studied so far. In case of the electron-transfer protein cytochrome c, electronic structure calculations helped clarify the intriguing nature of the Fe-S bond at the active site [40] whereas for cytochrome P450, steps of the enzymatic reaction were investigated [41-44]. The P450 family of enzymes is involved in the metabolism of endogenous and xenobiotic compounds and this work can therefore be of potential use in toxicology research. 

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... 

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