The reversal of phenylarsenoxide inhibition of keto acid oxidation in mitochondrial and bacterial suspensions by lipoic acid and other disulphides

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Abstract
Inhibition of pyruvate oxidation in suspensions of Aerobacter aerogenes cells and of isolated mitochondria from rat heart and liver by phenylarsenoxide is prevented by an excess of lipoic acid, whereas inhibition due to certain bivalent cations is not. In both systems inhibition persists when the bacteria and mitochondria are recovered and resuspended in fresh media in the absence of the inhibitor. Persistent inhibition due to preincubation with phenylarsenoxide, but not with the metal ions, is reversed by lipoic acid and by certain other disulphides. 2, 3-Dimercaptopropan-1-ol prevents the inhibition of pyruvate oxidation by phenylarsenoxide and by bivalent cations in both mitochondria and bacterial cells. In aerobic suspensions of mitochondria and bacteria disulphides such as lipoic acid are reduced rapidly to dithiols. Reduction is inhibited by Co2+, Ni2+, Cd2+and Zn2+, but not by phenylarsenoxide. It is concluded that the inability of lipoic acid to prevent the action of the metal ions on pyruvate oxidation is due to the inhibition of its reduction to the effective dithiol.