Redistribution of the flux-control coefficients in mitochondrial oxidative phosphorylations in the course of brain edema.
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.
Rigoulet
M
M
Institut de Biochimie Cellulaire et Neurochimie du CNRS, Bordeaux, France.
Averet
N
N
Mazat
J P
JP
Guerin
B
B
Cohadon
F
F
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism*; D007700:Kinetics; D008314:Malonates / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009257:Nafronyl / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D013385:Succinate Dehydrogenase / Q000378:metabolism
D008314:Malonates; D009257:Nafronyl; C030290:malonic acid; D013385:Succinate Dehydrogenase