Substrate Dependent Reversibility of Inhibition by β-Thujaplicin of Glucose and Acetate Respiration in Saccharomyces cerevisiae

Attempts to determine the rate of uptake of β-thujaplicin (TH) and its 1:1 rupric chelate (CuT⁺) in yeast cells showed in both cases a very rapid equilibration. In the concentration range where respiration is inhibited, most of the TH added was still present in the extracellular fluid, while CuT⁺ was almost completely removed. The inhibition of glucose respiration by TH was Completely removed when the cells were repeatedly washed, while inhibition of acetate respiration remained. Washing of CuT⁺ inhibited cells did not release the inhibition of either glucose or acetate respiration. The succinic acid dehydrogenase activity was the same in homogenates of both CuT⁺ and TH inhibited cells as in homogenates of non-inhibited cells. Prior to homogenization acetate respiration was inhibited by 60 to 70 per cent by both inhibitors. Alcohol dehydrogenase activity was likewise not affected by TH and CuT⁺. The formation of acetyl coenzyme A was inhibited by both TH and CuT⁺ to about the same extent as the respiration of acetate. It is concluded that TH inhibits the acetate respiration by inhibiting the formation of acetyl coenzyme A from acetate. The same site of action is plausible also for CuT⁺ but in that case, additional sites of inhibition may also be located in the reactions in the Krebs cycle.