Cd2+ and Cu2+ ions inhibit cytochrome oxidase in the respiratory chain of liver mitochondria

Abstract

We have determined earlier that the main target of direct toxic action of two metal ions Cd2+ and Cu2+ (5 mM) on oxidative phosphorylation is within the respiratory subsystem. With the aim of localizing the effects of these ions in the respiratory chain, modular kinetic analysis on the level of the respiratory subsystem was performed. To this end, the oxidative phosphorylation system was conceptually divided into modules around different intermediates – coenzyme Q (CoQ) (CoQ-reducing and CoQ-oxidizing modules) and cytochrome c (cytochrome c-reducing and cytochrome c-oxidizing modules). Experiments were performed on rat liver mitochondria respiring with succinate (+ rotenone) in state 3. By the changes induced by ions of both metals in the kinetics of the modules we determined that Cd2+ and Cu2+ did not have any effect on succinate dehydrogenase (SDH) and cytochrome bc1. The inhibition of the respiratory subsystem in both cases was caused by the action of these ions on cytochrome oxidase (COX). Keywords: liver mitochondria, kinetic analysis, respiratory chain, cadmium ions, copper ions