Mitochondrial respiratory electron-transfer system

FIGURE 19-1 Biochemical anatomy of a mitochondrion. The convolutions (cristae) of the inner membrane provide a very large surface area. The inner membrane of a single liver mitochondrion may have more than 10,000 sets of electron-transfer systems (respiratory chains) and ATP synthase molecules, distributed over the membrane surface. Heart mitochondria, which have more profuse cristae and thus a much larger area of inner membrane, contain more than three times as many sets of electron-transfer systems as liver mitochondria. The mitochondrial pool of coenzymes and intermediates is functionally separate from the cytosolic pool. The mitochondria of invertebrates, plants, and microbial eukaryotes are similar to those shown here, but with much variation in size, shape, and degree of convolution of the inner membrane. 

Before we try to understand the mechanism of oxidative phosphorylation, let s first look at the molecules that carry out this complex process. Embedded within the mitochondrial inner membrane are electron transport systems. These are made up of a series of electron carriers, including coenzymes and cytochromes. All these molecules are located within the membrane in an arrangement that allows them to pass electrons from one to the next. This array of electron carriers is called the respiratory electron transport system (Figure 22.7). As you would expect in such sequential oxidation-reduction reactions, the electrons lose some energy with each transfer. Some of this energy is used to make ATP. 

In biochemical systems, acid-base and redox reactions are essential. Electron transfer plays an obvious, crucial role in photosynthesis, and redox reactions are central to the response to oxidative stress, and to the innate immune system and inflammatory response. Acid-base and proton transfer reactions are a part of most enzyme mechanisms, and are also closely linked to protein folding and stability. Proton and electron transfer are often coupled, as in almost all the steps of the mitochondrial respiratory chain. 

Cytochrome c, a small heme protein (mol wt 12,400) is an important member of the mitochondrial respiratory chain. In this chain it assists in the transport of electrons from organic substrates to oxygen. In the course of this electron transport the iron atom of the cytochrome is alternately oxidized and reduced. Oxidation-reduction reactions are thus intimately related to the function of cytochrome c, and its electron transfer reactions have therefore been extensively studied. The reagents used to probe its redox activity range from hydrated electrons (I, 2, 3) and hydrogen atoms (4) to the complicated oxidase (5, 6, 7, 8) and reductase (9, 10, 11) systems. This chapter is concerned with the reactions of cytochrome c with transition metal complexes and metalloproteins and with the electron transfer mechanisms implicated by these studies. 

The oxidation by 02 of [H] (either as NADH or FADH, succinate or directly as active acetic acid) occurs via a sequence of electron transfer steps between redox components being incorporated (more or less deeply) into the inner mitochondrial membrane. As is shown in Fig. 11 in the above mentioned electron transport chain, referred to as respiratory chain, the electronic energy is successively decreased step by step. Oxygen is introduced only into the last step of the chemical events in the respiratory chain. Nature has developed a special enzyme system, the cytochrome oxidase, for the realization of oxygen reduction to water. It is assumed that this enzyme system provides the indispensible cooperation of four electrons and protons, respectively, which is required for oxygen reduction ... 

Proton-coupled electron transfer (PCET) is known to play an important role in a variety of biological processes, including microbial iron transport by ferric enterobactin, enzyme catalysis in systems such as fumarate reductase and nitrate reducatase, and dioxygen binding by the non-heme iron protein hemerythrin. " As such, pH-dependent electrochemical studies can play an important role in unraveling these mechanisms. The most heavily studied biological system known to involve PCET is cytochrome c oxidase, the terminal electron-transfer complex of the mitochondrial respiratory chain, which catalyzes the reduction of molecular oxygen to water. ... 

In many microorganisms and in the mitochondrion of eukaryotic cells, the driving force is provided by electron transfers generated by the oxidation of a substrate in a process called respiration. For example, the mitochondrial respiratory system is made of four membrane-bound complexes... 

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