Effect of tolbutamide on the metabolism of Tetrahymena.

Abstract

AbstractTolbutamide partially inhibited the growth but increased the glycogen content of Tetrahymena pyriformis in logarithmically growing cultures. Tolbutamide slightly increased 14CO2 production from [1‐14C] and [6‐14HC] glucose and [2‐14C] pyruvate, but had little effect on the oxidation of [1‐14C] acetate when any of these substrates were added to the proteose‐peptone medium in which the cells had been grown. Measurement of 14CO2 production from [1‐14C] and [2‐I4C]‐glyoxylate showed that this substrate was primarily oxidized via the glyoxylate cycle, with little if any oxidation occurring via the peroxisomal glyoxylate oxidase. Addition of tolbutamide inhibited the glyoxylate cycle as indicated by a marked reduction in label appearing in CO2 and in glycogen from labeled acetate. In control cells, addition of acetate strongly inhibited the oxidation of [2‐14C]‐pyruvate whereas addition of pyruvate had little effect on the oxidation of [1‐14C]‐acetate. Acetate was more effective than pyruvate in preventing the growth inhibitory and glycogen‐increasing effects of tolbutamide. The data suggest that one effect of tolbutamide may be to interfere with the transfer of isocitrate and acetyl CoA across mitochondrial membranes.