ELECTRON TRANSPORT 659 



Effects of Combinations of Arsenicals and Thiols 



Recent investigations by Sanadi and his collaborators have cast new 

 light on the actions of the arsenicals on electron transport and phosphoryl- 

 ation. The effects of arsenicals on enzymes, metabolism, function, and 

 growth had almost invariably been found to be prevented or reversed by 

 dithiols such as dimercaprol (BAL), and this has led to the clinical use 

 of BAL in arsenical poisoning. However, certain processes in liver and 

 heart mitochondria are altered much more potently by equimolar mixtures 

 of arsenite and BAL (i. e., by the arsenite-BAL complex) than by arsenite 

 alone. Thus arsenite-BAL is a much more effective uncoupler than arsenite 

 in many systems (Fluharty and Sanadi, 1960, 1961); it stimulates mito- 

 chondrial ATPase activity more (Fluharty and Sanadi, 1960), inhibits 

 the ATP:P^^ exchange more readily (Fluharty and Sanadi, 1961), and 

 causes greater mitochondrial swelling (Fluharty and Sanadi, 1962 b). 

 The effects on oxidative phosphorylation are particularly well seen in 

 the work of Fletcher and Sanadi (1962) on beef heart mitochondria oxidiz- 

 ing various substrates (see accompanying tabulation). In these experiments 



Malate-pyruvate ^-Hydroxybutyrate Glutamate 



arsenite was 0.1 mM and BAL was 0.11 mM. In some cases, as here, Og 

 uptake is depressed more by arsenite-BAL than by arsenite, but in others 

 the BAL may antagonize the inhibition by arsenite. If BAL is added in 

 excess, the potentiating effect seen at equimolar concentrations disappears 

 (see accompanying tabulation) (Fletcher et al., 1962). These results were 



Arsenite BAL ^ ^ , t. /^ 



, 1,^. , ,^v O2 uptake P : 



(mM) {mM) ^ 



