THE EFFECT OF DISULPHIDES ON MITOCHONDRIAL OXIDATIONS.

1. Nicotinamide nucleotide-linked mitochondrial oxidations were inhibited by the disulphides NNN'N'-tetraethylcystamine, cystamine and cystine diethyl ester, whereas l-homocystine, oxidized mercaptoethanol, oxidized glutathione, NN'-diacetylcystamine and tetrathionate were only slightly inhibitory. Mitochondrial oxidations were not blocked by the thiol cysteamine. 2. NAD-independent oxidations were not inhibited by cystamine. The oxidation of choline was initially stimulated. 3. The inactivation of isocitrate, malate and beta-hydroxybutyrate oxidation of intact mitochondria could be partially reversed by external NAD. For the reactivation of alpha-oxoglutarate oxidation a thiol was also required. 4. A leakage of nicotinamide nucleotides from the mitochondria is suggested as the main cause of the inhibition. In addition, a strong inhibition of alpha-oxoglutarate dehydrogenase by cystamine was observed. A mixed disulphide formation with CoA and possibly also lipoic acid and lipoyl dehydrogenase is suggested to explain this inhibition.