THE EFFECT OF p-DIMETHYLAMINOBENZENEDIAZO SODIUM SULFONATE (DAS) ON THE ENZYMATIC REACTIONS OF INTERMEDIARY CARBOHYDRATE METABOLISM

¹ University of Chicago Toxicity Laboratory and the Department of Pharmacology, University of Chicago, Chicago, Illinois

1. In vitro studies demonstrated that dimethylaminobenzenediazo sodium sulfonate (DAS) inhibits the succinic dehydrogenase activity of rat liver and kidney after a preliminary incubation of the enzyme with the rodenticide. However, no inhibition of the succinic dehydrogenase activity of the tissues of rats was observed at 5 hours after the administration of 30 mgm./kgm. of DAS. No inhibitory effect by DAS was observed on cytochrome oxidase, malic dehydrogenase and fumarase.

2. The oxidation of glucose by rat brain homogenates was inhibited in vitro by concentrations of DAS above 1 x 10^-6 M; however, no depression of glucose oxidation by brain tissue from DAS-poisoned rats was observed. The respiration of liver tissue was inhibited in vitro and in vivo by DAS. The toxic agent had no effect on the rate of anaerobic glycolysis by rat liver slices and brain homogenates.

3. DAS had no effect on the oxidation of fumarate, succinate, malate and oxalacetate by liver slices taken from rats 5 hours after the administration of 30 mgm./kgm. of the toxic compound. However, the stimulation of respiration of liver slices by pyruvate and citrate was depressed both in vitro and in vivo by DAS.

4. The phosphocreatine of rat liver and kidney tissue was depleted within 5 hours after the administration of 30 mgm./kgm. of DAS while the phosphocreatine of skeletal muscle and cardiac muscle was unaffected by this dose of the compound. Other changes in the distribution of acid-soluble phosphorus compounds in the liver and kidney of DAS-poisoned rats consisted of a slight decrease in glucose-1-phosphate and a small increase in glucose-6-phosphate, phosphopyruvate and triose phosphate.

5. DAS exerted a marked inhibitory effect on the aerobic phosphorylation of creatine by rat, mouse and guinea pig kidney homogenates. Aerobic phosphorylation was also inhibited in the tissues of animals given lethal doses of DAS. The inhibition in vivo was dependent upon the dose of the compound administered and varied with the species susceptibility to DAS.