THE EFFECT OF DISULPHIDES ON MITOCHONDRIAL OXIDATIONS

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Abstract
Nicotinamide nucleotide-linked mitochondrial oxidations were inhibited by the disulphides NNN[image]N[image]-tetraethylcystamine, cystamine and cystine diethyl ester, whereas L-homocystine, oxidized mercaptoethanol, oxidized glutathione, NN[image]-diacetylcystamine and tetrathionate were only slightly inhibitory. Mitochondrial oxidations were not blocked by the thiol cysteamine. NAD-independent oxidations were not inhibited by cystamine. The oxidation of choline was initially stimulated. 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. 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.