Respiratory chain components

L-selegiline alters the redox state of ubiquinone, suggesting that the flow of electrons is impaired in the respiratory chain. Furthermore, a decrease in ubiquinone levels has been observed, whereas ubiquinol (reduced ubiquinone) concentrations are increased in the striatum. Ubiquinol levels have been shown to augment as a result of impaired mitochondrial respiration. For example, ubiquinol concentrations were demonstrated to increase in tubular kidney cells exposed to complex IV inhibitors and in disease states with defects in respiratory chain components. These results are also consistent with the hypothesis that L-selegiline enhances 02 formation by altering the rate of electron transfer within the respiratory chain leading to increases in SOD activities in the mouse striatum. 

In this account we will review the structural and functional properties of the respiratory chain components, as they are known from studies with intact mitochondria, vesicles of the inner mitochondrial membrane (submitochondrial particles), or isolated complexes. The latter may additionally be reconstituted into liposomal membranes. To some extent we will also review the knowledge on the integrated functions of the respiratory chain with main emphasis on proton translocation and essential thermodynamic and kinetic properties. 

The area of the inner membrane of rat liver mitochondria has been estimated to be about 40 m g of mitochondrial protein [13,80]. Together with the data of Table 3.2, this means that, on average, the above number of respiratory chain components occupies a membrane area of approx. 900 nm (e.g., a square with a side... 

The arrangement of components of the electron transport chain was deduced experimentally. Since electrons pass only from electronegative systems to electropositive systems, the carriers react according to their standard redox potential (Table 14-2). Specific inhibitors and spectroscopic analysis of respiratory chain components are used to identify the reduced and oxidized forms and also aid in the determination of the sequence of carriers. 

Impaired respiration also blocks the transfer of electrons along the respiratory chain, causing reduction of upstream respiratory chain components, which then react with oxygen to form the superoxide anion radical (Fig. 6). Increased ROS formation can damage mtDNA and respiratory polypeptides thus further impairing respiration. ROS may also play a role in necroinflammation and fibrosis (Pessayre and Fromenty 2005). 

Place the following respiratory-chain components in their proper sequence. Also, indicate which are mobile carriers of electrons. 

Cyanide blocks the transfer of electrons from cytochrome oxidase to O2. Therefore, all the respiratory-chain components become reduced and electron transport ceases consequently, oxidative phosphorylation stops. An artificial electron acceptor -with an appropriate redox potential, such as methylene blue, can reoxidize some components of the respiratory chain, reestablish a proton gradient, and thereby restore ATP synthesis. The methylene blue takes the place of cytochrome oxidase as a means of transferring electrons to O2, which remains the terminal electron acceptor. 

Upstream from the inhibitor, reduced respiratory-chain components will accumulate downstream, oxidized components will be present. The point of inhibition is the crossover point. 

The degree of conservation, in terms of subunit composition and protein sequence, between mammalian respiratory chain complexes and those characterized from fungi and other organisms depends on the subunit and complex being considered (detailed in specific sections below), but in general, those subunits which are known to have a central role in electron transport are well conserved in terms of protein sequence and, where known, tertiary structure. For these subunits, a dear relationship to bacterial respiratory chain components can also be seen, which leads to the condusion that the mitochondrial respiratory chain complexes have evolved and adapted from those of the symbiotic bacterial ancestor of the mitochondrion [23]. Mitochondrial complexes have in most cases acquired many additional subunits whose function remains obscure. 

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