The steady state activity of succinate dehydrogenase in the presence of opposing effectors - I. The effect of l malate and CoQH₂ on the enzymic activity

Succinate dehydrogenase is subjected to positive and negative modulation. The negative modulators oxaloacetate and D- or L-malate transform the enzyme into a nonactive complex in which oxaloacetate is bound. The deactivation by malate involves its oxidation by the succinate dehydrogenase which then deactivates the enzyme. In the present study we measured the activity of succinate dehydrogenase in the presence of two opposing effectors, L-malate as deactivator and CoQH₂ as an activator. With these opposing effectors present, the catalytic activity of succinate dehydrogenase assumes a steady state, the level of which is a function of the concentration of the two effectors. At low concentration of L-malate all of the succinate dehydrogenase activity is protected by CoQH₂, while at saturating malate concentrations only 60-70% of activity is protected. Kinetic analysis of the approach to the steady state indicates that the protective effect of CoQH₂ is not due to its activator property but due to its ability of reduce the enzyme. This was verified by carrying out a redox titration of succinate dehydrogenase activity in the presence of L-malate. A redox active component was characterized with E′ = +25 mV and n = 1.8. When this component is reduced, L-malate cannot deactivate the succinate dehydrogenase, but when in the oxidized state the enzyme is susceptible to such deactivation. It is proposed that this group participates in the regulation of the activity of succinate dehydrogenase in the mitochondria.