Cytochrome redox systems

The cytochromes are another group of haem proteins found in all aerobic forms of life. Cytochromes are electron carriers involving a Fe(ii)/Fe(m) redox system. They are a crucial part of the electron transfer reactions in mitochondria, in aspects of the nitrogen cycle, and in enzymic processes associated with photosynthesis. 

Table 12 shows redox properties of some redox systems of biochemical nature. Generally, the redox potentials are modest, cytochrome P450 possibly being an exception. If cytochrome P450 functions as an electron transfer oxidant towards xenobiotic molecules, it is necessary to postulate a considerably higher potential (1.3-1.8V) from considerations of the Marcus theory (Eberson, 1990). 

Malmslrom, B. G. The mechanism of dioxygen reduction in cytochrome c oxidase and laccase. In Oxidases and Related Redox Systems (King, T. E., Mason, H. S., Morrison, M., eds.), Oxford-New York, Pergamon Press, 1981... 

In bacteria some cytochromes b and dt serve as terminal electron carriers able to react with 02, nitrite, or nitrate, while others act as carriers between redox systems.141-1433 The aldehyde heme a is utilized by animals and by some bacteria in cytochrome c oxidase, a complex enzyme whose three-dimensional structure is known (see Fig. 18-10) and which is discussed further in Chapter 18. 

However, the changes in environment which occurred with the change from a reductive to an oxidative atmosphere rendered iron sulfide-based redox systems inconvenient, as they were very sensitive to (irreversible) oxidation. We saw in earlier chapters the facile formation of porphyrin and phthalocyanines from relatively simple precursors, and these systems were adopted for the final steps of electron transfer in oxidative conditions. The occurrence of iron centres in planar tetradentate macrocycles is ubiquitous, and metalloproteins containing such features are involved in almost every aspect of electron transfer and dioxygen metabolism. A typical example is seen in the electron transfer protein cytochrome c (Fig. 10-10). 

The mechanism of electron transfer reactions in metal complexes has been elucidated by -> Taube who received the Nobel Prize in Chemistry for these studies in 1983 [xiv]. Charge transfer reactions play an important role in living organisms [xv-xvii]. For instance, the initial chemical step in -> photosynthesis, as carried out by the purple bacterium R. sphaeroides, is the transfer of electrons from the excited state of a pair of chlorophyll molecules to a pheophytin molecule located 1.7 mm away. This electron transfer occurs very rapidly (2.8 ps) and with essentially 100% efficiency. Redox systems such as ubiquinone/dihydroubiquinone, - cytochrome (Fe3+/Fe2+), ferredoxin (Fe3+/Fe2+), - nicotine-adenine-dinucleotide (NAD+/NADH2) etc. have been widely studied also by electrochemical techniques, and their redox potentials have been determined [xviii-xix]. 

Regio- and stereospecific monohydroxylations of elaborated molecules have been achieved with monooxygenases that are in most cases membrane-bound cytochrome P450 enzymes. Because these are coupled with a complex redox system for electron transport from NADPH, the reactions are preferably carried out with whole cells [52], The same is true for enantioselective enzymatic epoxida-tions. An impressive example documented in eq. (6) is the preparation of 18 in 78 % yield and high ee [53]. 

R429 D. F. V. Lewis and P. Hlavica, Interaction between Redox Partners in Various Cytochrome P450 Systems Functional and Structural Aspects , Biochim. Biophys. Acta, 2000,1460, 353... 

The electrons provided in the light reaction, however, may also be directly exported from the cells and used to reduce a variety of extracellular substrates. This electron export is effected by surface enzymes (called transplasmamembrane reductases) spanning the plasmamembrane from the inside surface to the outside. They transfer electrons from an internal electron donor [chiefly NADH and NADPH see Crane et al. (1985)] to an external electron acceptor. Direct reduction of extracellular compounds by transplasmamembrane electron transport proteins is prevalent in all cells thus far examined (Fig. 2.2). Although the function of this redox system is still subject to speculation, in phytoplankton it shows considerable activity, relative to other biochemical processes. A host of membrane-impermeable substrates, including ferricyanide, cytochrome c, and copper complexes, are reduced directly at the cells surface by electrons originating from within the cell. In phytoplankton, where the source of electrons is the light reactions of photosynthesis, the other half-redox reaction is the evolution of ()2 from H20. In heterotrophs, the electrons originate in the respiration of reduced substances. 

Perhaps the three most important redox systems in bioinorganic chemistry are (I) high spin, tetrahedral Fe(II)/Fe(III) in rubredoxin, ferredoxin, etc. (2) low spin, octahedral Fe(II)/Fe(IlI) in the cytochromes and (3) pseudotetrahedral Cu(I)/Cu(II) in the blue copper proteins, such as slellacyanin, plastocyanin, and azurin. Gray94 has pointed out that these redox centers are ideally adapted for electron exchange in that no change in spin state occurs. Thus there is little or no movement of the ligands—the Franck-Condon activation barriers will be small. 

Electron transfers are key steps in many enzymatic reactions involving the oxidation or reduction of a bound substrate. Relevant examples include cytochrome c oxidase (O2 — 2H2O) and nitrogenase (N2 2NH3). To reinforce the claim that electron-transfer steps are of widespread importance, several other redox systems, representative of diverse metabolic processes, will be mentioned here. 

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