Multiple Effects of Amobarbital on Ehrlich Ascites Tumor Cells. Inhibition of Pyruvate Dehydrogenase

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Abstract
The inhibition of the proliferation of hyperdiploid Ehrlich ascites tumor cells [mouse] in suspension cultures by amobarbital is coupled to an increased glycolytic activity as shown by lactic acid production and glucose consumption. Higher concentrations of amobarbital than 1 mM enhance the ATP/ADP ratio of the total cell. The actual activity of pyruvate dehydrogenase of intact cells is completely inhibited in the presence of 2 mM amobarbital as was shown by the 14CO2 evolution from [1-14C]pyruvate or the incorporation of 14CO2 into the total lipid fraction of the cells from [U-14C]pyruvate or from [U-14C]lactate. The pyruvate dehydrogenase complex from Ehrlich ascites tumor cells is completely inhibited by 1 mM amobarbital in vitro. The activity of .alpha.-oxoglutarate dehydrogenase is inhibited by amobarbital as was shown by measuring the 14CO2 evolution from [1-14C]glutamate with intact cells. The inhibition of pyruvate dehydrogenase in the presence of amobarbital apparently is the result of a direct action on the enzyme and the consequence of a change in the cellular redox state or its energy charge.