Respiratory chain sites

Figure 12-7. Proposed sites of inhibition (0) of the respiratory chain by specific drugs, chemicals, and antibiotics. The sites that appear to support phosphorylation are indicated. BAL, dimercaprol. TTFA, an Fe-chelating agent. Complex I, NADHiubiquinone oxidoreductase complex II, succinate ubiquinone oxidoreductase complex III, ubiquinohferricytochrome c oxidoreductase complex IV, ferrocytochrome ctoxygen oxidoreductase. Other abbreviations as in Figure 12-4.

In the thermodynamically redox-stable resting state, CcOs all Cu ions are in the Cu state and all hemes are Fe . From this state, CcOs can be reduced by one to four electrons. One-electron reduced CcOs are aerobically stable with the electron delocalized over the Cua and heme a sites. The more reduced forms—mixed-valence (two-electron reduced), three-electron reduced, and fully (four-electron) reduced—bind O2 rapidly and reduce it to the redox level of oxide (—2 oxidation state) within <200 p-s [Wikstrom, 2004 Michel, 1999]. This rate is up to 100 times faster than the average rate of electron transfer through the mammalian respiratory chain under normal... 

It is interesting that a new group of fungicides based on the natural products from the fungus Strobilurus tenacellus also inhibit mitochondrial respiration at the site of complex III (bei-complex) of the respiratory chain (see Chapter 4). Recently synthesised compounds from within this class are showing interesting insecticidal effects. 

Finally, the intermediate P-to-O ratio obtained with succinate indicates that a coupling site occurs in complex III, but probably not in complex II. Thus, the respiratory chain appears to have three distinct coupling sites for ATP synthesis. 

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