Metabolic Inhibitors: Volume I

Although amino acids under certain conditions had been known for a long time to be toxic to growth of certain organisms, specific reversals of inhibitory effects by a particular metabolite have been observed only since 1935. For example, 0-alanine was observed to be potent as a growthstimulating agent for yeast only in the absence of asparagine, the presence of which was essential for the development of the specific assay in the discovery of pantothenic acid (1). The antagonism is mutual, since not only does asparagine prevent the conversion of ^-alanine to pantothenic acid, but β-alanine also exerts a toxic effect on yeast, which is prevented by asparagine or by aspartic acid (β). Ethionine, prepared and tested for its ability to replace methionine in stimulating the growth of rats on a cysteinedeficient diet, proved to be toxic, but methionine supplementation offset the apparent toxicity (8). In a study of 2- and 5-methyltryptophan as replacements for tryptophan in a deficient diet in the growth of rats, these compounds exerted a depressing effect upon growth, but this effect of 5-methyltryptophan was not noted with a complete diet (4).