Respiratory inhibitors action sites

Respiratory inhibitors not only deprive the organism of the major end-product, ATP, but may interfere with the production of other vital synthetic intermediates. Several sites of action have been identified for fungicides. 

Figure 15.9 Sites of action of some respiratory inhibitors and artificial electron acceptors. 

Qo site inhibitors of class 1 have been discovered during a systematic search for new antibiotic agents from basidiomycetes which was started in 1976 [9], The fungicidal activity of strobilurin A and the localization of its site of action in the respiratory chain... 

Crossover point. The precise site of action of a respiratory-chain inhibitor can be revealed by the crossover technique. Britton Chance devised elegant spectroscopic methods for determining the proportions of the oxidized and reduced forms of each carrier. This determiniation is feasible because the forms have distinctive absorption spectra, as illustrated in the adjoining graph for cytochrome c. You are given a new inhibitor and find that its addition to respiring mitochondria causes the carriers between NADH and QH2 to become more reduced and those between cytochrome c and O2 to become more oxidized. Where does your inhibitor act ... 

The respiratory chain. Boxes indicate the composition of complexes I to IV. Electron flow is shown by arows. Sites of action of some inhibitors are labeled 1, 2 and 3, and indicated by horizontal bars. Sites 2 and 3 are also coupled with ATP synthesis, i.e. according to the chemiosmotic theory, each of these stages of electron transfer (from cytochrome b to cytochrome c, and from cytochrome to oxygen) provides enough energy to generate a proton gradient for the synthesis of one molecule of ATP. The first site of ATP synthesis may not be identical with inhibition site 1 as shown here, but it is known to exist on the ubiquinone side (rather than the substrate side) of complex I. 

---