Inhibition of mammalian succinate dehydrogenase by carboxins.

Carboxin (5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide), a systemic fungicide, is known to inhibit the oxidation of succinate selectively in a variety of fungi and bacteria. Except for one report, the action of carboxin and of structurally related oxathiin derivatives on mammalian succinate dehydrogenase have not been investigated, however. In the present study, the inhibition of succinate oxidation by a number of carboxin derivatives have been studied using inner membrane preparations, purified particulate preparations (Complex II), and soluble preparations from beef heart. The site of action of carboxins has been studied by using a variety of electron acceptors. It has been concluded that carboxins inhibit mammalian succinate dehydrogenase by reacting at the same site as thenoyltrifluoroacetone but are effective at far lower concentrations. The maximal extent of inhibition by carboxins varies with the type of catalytic assay used and, in general, parallels the extent of inactivation brought about by cyanide, as if both types of agents modified the environment of an iron-sulfur component in the enzyme, presumably the superoxidized (HiPIP) Fe-S cluster.