Electron-transport system mitochondrial respiratory

It has been shown recently that the mitochondrial electron transport system contains at least three different fe-type cytochromes 178). Two of these cytochromes are found in complex III, and under appropriate conditions are reducible with substrates. The third 6-type cytochrome was discovered by Davis et al. 178), and shown to fractionate exclusively into complex II. At 77°K, the cytochrome 6 of complex II exhibits a double a band at 557.5 and 550 nm, a prominent band at 531 nm, and a Soret band at 422 nm (Fig. 29). Cytochrome 6557.5 appears to have a low reduction potential. It is not detectably reduced by succinate in either complex II or respiratory particles, but its dithionite reduced form is rapidly oxidized by either fumarate or ubiquinone. The role of this cytochrome in mammalian mitochondria is not known. Davis et al. 178) have suggested that it might be an electron entry point for an unknown ancillary tributary of the respiratory chain. Further, Bruni and Racker 179) have shown that a preparation of cytochrome 6 is required for reconstitution of succinate-ubiquinone reductase activity (see below). 

These findings are consistent with impaired fatty-acid oxidation reduced mitochondrial entry of long-chain acylcarnitine esters due to inhibition of the transport protein (carnitine palmityl transferase 1) and failure of the respiratory chain at complex II. Another previously reported abnormality of the respiratory chain in propofol-infusion syndrome is a reduction in cytochrome C oxidase activity, with reduced complex IV activity and a reduced cytochrome oxidase ratio of 0.004. Propofol can also impair the mitochondrial electron transport system in isolated heart preparations. 

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 contrast to common usage, the distinction between photosynthetic and respiratory Rieske proteins does not seem to make sense. The mitochondrial Rieske protein is closely related to that of photosynthetic purple bacteria, which represent the endosymbiotic ancestors of mitochondria (for a review, see also (99)). Moreover, during its evolution Rieske s protein appears to have existed prior to photosynthesis (100, 101), and the photosynthetic chain was probably built around a preexisting cytochrome be complex (99). The evolution of Rieske proteins from photosynthetic electron transport chains is therefore intricately intertwined with that of respiration, and a discussion of the photosynthetic representatives necessarily has to include excursions into nonphotosynthetic systems. 

Polymorphonuclear leucocytes (PMNs) employ a system comprising myeloperoxidase, hydrogen peroxide, and a halide factor to kill microorganisms and tumour cells. This process is sometimes loosely called the respiratory burst , which refers to the sudden rise in oxygen consumption by the phagocytosing neutrophils that is independent of the mitochondrial electron transport chain. 

Figure 18-19 The ammonia oxidation system of the bacterium Nitrosomonas. Oxidation of ammonium ion (as free NH3) according to Eq. 18-17 is catalyzed hy two enzymes. The location of ammonia monooxygenase (step a) is uncertain but hydroxylamine oxidoreductase (step b) is periplas-mic. The membrane components resemble complexes I, III, and IV of the mitochondrial respiratory chain (Fig. 18-5) and are assumed to have similar proton pumps. Solid green lines trace the flow of electrons in the energy-producing reactions. This includes flow of electrons to the ammonia monoxygenase. Complexes HI and IV pump protons out but complex I catalyzes reverse electron transport for a fraction of the electrons from hydroxylamine oxidoreductase to NAD+. Modified from Blaut and Gottschalk.315...

Mitchell, P., and J. Moyle, Stoichiometry of proton translocation through the respiratory chain and adenosine triphosphatase systems of rat liver mitochondria. Nature 208 147, 1965. The initial observations that electron transport moves protons outward across the mitochondrial inner membrane and that ATP hydrolysis does the same. 

In other membranes responsible for energy transduction, oxidation-reduction reactions are the basis for proton movement across the membrane. The classical example is found in mitochondria where electron flow through the respiratory system drives proton movement from the inner matrix to the intermembrane space. The resultant protonmotive force is used to drive ATP synthesis or to maintain mitochondrial membrane potential (negative inside). A similar association between electron transport in a membrane oxidation reduction chain and proton movement... 

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 ... 

Rotenone is an alkaloid botanical pesticide isolated from plants (Denis sp. or Lonchocarpus sp.). It blocks mitochondrial electron transport. It is associated with dermatitis and mucous membrane irritation in humans and is very potent in fish. In humans, intoxication is rare but when present is directed toward the respiratory system. Rotenone is used as a topical ectoparasiticide. As mentioned in the text, it has been implicated as possibly having a role in Parkinson s disease. The newest and by far safest class of insecticides available today are the insect growth inhibitors, such as methoprene (PreCor ), and chitin synthesis inhibitors, such as lufenuron (Program ). 

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