METABOLITE ANTAGONISTS 229 



tion. This is due to the synthesis of the metabohte by the organism. 

 Sulfanilamide inhibits the growth of Aspergillus niger, but the fun- 

 gus overcomes this inhibition as the time of incubation is prolonged 

 (Hartelius, 194G). The concentration of a metabolite in the control 

 cultures should be less than the amount which allows maximum growth, 

 because of the nonlinear response of an organism to the metabolite at 

 high concentrations. 



The composition of the medium is an important consideration in any 

 investigation of metabolite antagonism. If adequate amounts of a 

 natural metabolite are present, the action of an inhibitor may be over- 

 looked. Synthetic media should be used. The composition of the 

 medium used may also affect the action of an inhibitor in another way. 

 If metabolite A is transformed into metabolite B by an organism, the 

 presence of metabolite B in sufficient amount for optimum growth may be 

 expected to nullify any amount of an antagonist for metabolite A. An 

 antagonist of metabolite B, however, would exhibit normal competitive 

 inhibition, Shive and Macow (1946) have pointed out that, by the use 

 of a suitable series of inhibitors, it is possible to follow the transformations 

 of a given metabolite step by step. These authors designate this use of 

 metabolite antagonists as inhibition analysis. Rydon (1948) found 

 Bacterium typhosum to synthesize tiyptophane by the following steps: 

 anthranilic acid — > indole — > tryptophane. The 2- and 4-methylanthran- 

 ihc acids were potent inhibitors against anthranilic acid but not against 

 indole or tryptophane. Certain analogues of indole and tryptophane 

 were inhibitors of these metabolites. 



In discussing metabolite antagonists in a general way, it should be 

 borne in mind that these compounds may inhibit only certain organisms, 

 or a particular organism only under certain conditions. For example, 

 desthiobiotin is a biotin antagonist for Ceratostomella pini and Lacto- 

 hacillus casei, while this compound replaces biotin for many strains of 

 Saccharomyces cerevisiae (Lilly and Leonian, 1944). Woolley (1944, 

 1946) is of the opinion that the established facts of inhibition and reversal 

 are more important than the hypotheses which are adopted to explain 

 these phenomena. However, the concept of competitive metabohte 

 antagonism has been very useful in correlating a vast amount of experi- 

 mental work in apparently unrelated fields. 



ANTIVITAMINS 



Antivitamins are known for all the water-soluble vitamins which have 

 been synthesized and for at least one of the fat-soluble vitamins (vitamin 

 K). 



p-Aminobenzoic acid antagonists. When the sulfonamides were intro- 

 duced into medicine, it was quickly found that serum and other natural 



