Mechanisms of Fatty Acid Toxicity for Yeast.

Neal, A. L. (Rutgers, The State University, New Brunswick, N.J.), Joan O. Weinstock, and J. Oliver Lampen. Mechanisms of fatty acid toxicity for yeast. J. Bacteriol. 90:126-131. 1965.-The internal pH of stationary- and log-phase yeast cells dropped quite rapidly when the cells were exposed to acetate buffers at pH 4 and 3, whereas no, or much less, acidification occurred with pyruvate or phosphate. Although inhibition of respiration and glycolysis was almost instantaneous when the cells were exposed to 0.2 m acetate at pH 4, the effect was not permanent and could be reversed by washing them with water or phosphate buffer. Irreversible inhibition did occur, however, at 0.5 m acetate under the same conditions; there was a marked decrease in several glycolytic enzyme systems, which undoubtedly contributed to the irreversible nature of the inhibition. In cell-free homogenates, various low-molecular-weight monocarboxylic acids exhibited about the same inhibitory effect on glycolysis; structural differences such as branching or unsaturation did not cause a marked change in their inhibitory effect. Also, glycolysis was much more sensitive to dicarboxylic acids such as succinate and phthalate than to acetate; phthalate was more inhibitory than succinate. This is in contrast with the noninhibitory nature of succinate and phthalate to whole cells, even at pH 4. Pyruvic acid decarboxylation was inhibited by phthalate but not by succinate. The greater toxic effect of phthalic acid may be due to the fixed steric configuration of its carboxyl groups, as compared with those of succinic acid.