Uncoupling of oxidative phosphorylation in rat liver mitochondria with desaspidin and related phlorobutyrophenone derivatives

Abstract

The effect of desaspidin, ortho-desaspidin, flavaspidic acid, nor-flavaspidic acid and desaspidinol on respiration and oxidative phosphorylation in rat liver mitochondria was studied. All these substances uncouple oxidative phosphorylation. Desaspidin and orthodesaspidin show maximum activity in the concentration 2–4 × 10 −6 M, the other substances in concentrations of 1.6–6.4 × 10 −5 M. Respiration is inhibited more or less distinctly by these concentrations, especially when glutamate or succinate are used as substrate. When pyruvate and malate are employed as the substrate, this effect is less pronounced. In a medium free of terminal phosphate acceptor respiration is stimulated by desaspidin and by flavaspidic acid to values corresponding to those obtained with phosphate acceptor or with 2:4-dinitrophenol. The connection between chemical structure and uncoupling effect as well as the possible connection between the former and the biological effects of the substances tested are discussed briefly.