This work describes the control exerted by
dicarboxylate carrier and
succinate dehydrogenase activities on the oxidative phosphorylations in rabbit brain mitochondria as an
edema develops. Vasogenic
edema leads to an uncompetitive inhibition of
succinate dehydrogenase activity and to a large decrease of oxidative phosphorylations linked to
succinate utilisation.
Naftidrofuryl treatment in vivo restores both a high
succinate dehydrogenase activity and a normal respiratory rate. In order to quantify the control of oxidative phosphorylations by the
succinate dehydrogenase step, we applied the control analysis (Kacser, H. and
Burns, J.A. (1973) in Rate Control of Biological Processes (Davies,
D.D., ed.), pp. 65-104, Cambridge University Press, London; Heinrich, R. and Rapoport, T.A. (1974) Eur. J. Biochem. 42, 89-95). By using two inhibitors, one (
phenylsuccinate) acting only on the
dicarboxylate carrier and another (
malonate) acting on both the
dicarboxylate carrier and the
succinate dehydrogenase, a method was developed to calculate the control coefficients of these two steps. The main result is that in mitochondria isolated from normal tissue
succinate dehydrogenase exerted no control, but in the course of
edema this enzymatic step became a controlling one: a transition from zero to a high control coefficient (0.5) was observed from the onset of intracellular
edema for the threshold value of water/dry-weight tissue of 4.6.