Modulation of the Activity of Succinate Dehydrogenase by Acetylation with Chemicals, Drugs, and Microbial Metabolites

Resumo

Abstract—The effects of acetylating and deacetylating compounds on the activity of succinate dehydrogenase, as well as on the membrane potential and calcium retention capacity of the isolated liver mitochondria, supported by the oxidation of succinate, has been investigated. The chemical reagent N-acetylimidazole, the microbial metabolite phenylacetate, along with the drugs acetylsalicylic acid and N-acetylcysteine, were used as acetylating compounds. These compounds reduced succinate dehydrogenase activity to different extents depending on the concentration and incubation conditions. An inhibitory analysis using intermediate electron carriers has shown that the ubiquinone-binding site of the enzyme undergoes acetylation. The inhibition was partially eliminated or prevented by pre-incubation of the mitochondria with nicotinamide adenine dinucleotide, a co-factor for deacetylation, and with polyamine spermidine, an acceptor of acetyl groups.