Complex I inhibitors as insecticides and acaricides.
Structurally diverse synthetic insecticides and acaricides had been shown to inhibit the proton-translocating NADH:ubiquinone oxidoreductase (complex I) activity. In addition, secondary metabolites from microbial and plant sources known to act on complex I exhibited biological activity against agricultural and environmental insect pests. Mechanistic studies indicated that these compounds interfered with ubiquinone reduction most likely at the same site(s) as the classical complex I inhibitors rotenone and piericidin A. Two approaches to characterize the mechanism of insecticidal/acaricidal complex I inhibitors were followed: enzyme kinetic studies and binding studies with radiolabeled inhibitors. Enzyme kinetic experiments were sometimes controversially interpreted regarding a competitive or non-competitive inhibitor mechanism with respect to the electron acceptor. In general, radioligand binding data with submitochondrial membranes were in line with the enzymological results but due to methodological drawbacks, saturation kinetic analyses were impossible. The main problems underlying many studies of inhibitor interaction with complex I were (i) the use of membrane-bound enzyme preparations and (ii) the physicochemical properties of the amphiphilic inhibitors with their strong tendency to accumulate in the membrane phase. A more recent approach to characterize inhbibitor interaction sites in complex I was the isolation of piericidin-resistant mutants of photosynthetic bacteria which produce a simpler homologue of mitochondrial NADH:Q oxidoreductase.
Lümmen
P
P
Hoechst Schering AgrEvo, D-65926 Frankfurt/Main, Germany. peter.luemmen@agrevo.com
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology*; D008925:Mites; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007306:Insecticides; D016660:NAD(P)H Dehydrogenase (Quinone)