The Effect of Amines on Yeast Poisoned by Iodoacetic Acid

The discovery by Lundsgaard (1) of the inhibitory effect of iodoacetic acid on tissue glycolysis and yeast fermentation has aroused interest in the possibility of its use in controlling the abnormally high glycolytic rate of the cancer cell. A knowledge of its mode of action is essential to progress in this direction. Lundsgaard believes that the iodoacetic acid acts by preventing the formation of phosphate esters. Yamasaki (2) supports this view, pointing out that the fermentation of hexosediphosphate by maceration juice is only slightly inhibited. Dudley (3) suggests that the inhibition may be due to destruction of glyoxalase, the action of which is strongly retarded by iodoacetic acid. WaldSchmidt-Leitz and his coworkers (4) have advanced evidence in support of the view that the inhibition is due to destruction of the sulfhydryl system. Finally, Barrenscheen and his coworkers (5) suggest that inhibition of glycolysis by iodoacetic acid and other substances, such as fluorides or oxalates, is due primarily to destruction of coenzyme, and particularly of that portion of the coenzyme complex represented by compounds of the type of adenylic acid pyrophosphate. Recently Zuckerkandl and Messiner-Klebermass (6) have reported that the addition of certain amines to yeast inhibited by iodoacetic acid produces a reactivation of fermentation. Thus, mand p-phenylenediamine, tyrosine, and an aminothiotriazole were found to reactivate, while urea, alanine, dimethylaniline, and guanidine, among others, did not. They explain this effect by a theory similar to that of Barrenscheen; namely, that inhibi-