PANTOTHENIC ACID 635 



isoserine and N-pantoyl-/?-aminoisobutyric acid, complete inhibition of 

 growth was not obtained regardless of the amount of inhibitor added. 75 

 For such organisms not completely inhibited, these compounds alone 

 partially and ineffectively replaced pantothenic acid in stimulating 

 growth; however, growth induced by pantothenic acid was readily in- 

 hibited by these compounds to a level corresponding to their own stimu- 

 latory effect, but no further. In cases of this type, almost complete 

 inhibition of growth was obtained before stimulation by the antimetab- 

 olite became apparent. The growth stimulated by any concentration of 

 these analogues was only a fraction of that obtained with maximal con- 

 centrations of pantothenic acid. 75 



The relative concentrations of these antimetabolites required to pro- 

 duce half-maximum and maximum inhibition varied considerably with 

 the various test organisms. The variation was from slightly more than 

 twofold for Leuconostoc mesenteroides P-60 to more than tenfold for 

 Lactobacillus arabinosus 17-5 and Lactobacillus casei. 75 



The condensation products of DL-pantolactone and the sodium salts 

 of DL-alanine, DL-a-aminoisobutyric acid, DL-norvaline, DL-valine, 

 DL-phenylalanine, DL-serine, L-asparagine, p-aminobenzoic acid and 

 sulfanilamide were inactive as inhibitory analogues of pantothenic acid 

 for Streptobacterium plantarum. However, the pantoyl derivatives of 

 norvaline and alanine were somewhat inhibitory against yeast, whether 

 the growth was stimulated by /^-alanine or by pantothenic acid. 77 



Pantothenones. Replacement of the carboxyl group of p-aminobenzoic 

 acid by various ketone groups resulted in compounds which competitively 

 inhibited the corresponding metabolite. 78 In determining whether or not 

 this type of alteration could be used extensively in obtaining antimetab- 

 olites, Woolley and Collyer 79 prepared phenyl-D-pantothenone and 

 found it to be somewhat effective in preventing competitively the utiliza- 

 tion of pantothenic acid for several organisms, as indicated in Table 29. 

 It should be noted that the inhibition indices are for half-maximum 

 inhibition. These values are usually only a fraction of those for maximum 

 inhibition of growth. For Escherichia coli, Saccharomyces cerevisiae, and 

 Endomyces vernalis, phenyl-D-pantothenone reduced the growth to half- 

 maximum at concentrations of 60, 33 and 39 y per cc, respectively, in the 

 presence of 0.04 y per cc of pantothenic acid. However, the inhibitions 

 were not reversed by supplementary pantothenic acid for these organisms, 

 which synthesize pantothenic acid. Saccharomyces cerevisiae requires, 

 of course, the /^-alanine portion in order to carry out this synthesis. It is 

 interesting to note in Table 29 that the toxicity of phenyl pantothenone 

 is reversed by pantothenic acid for a strain of Staphylococcus aureus, 

 which was found to grow w r ell without exogenous pantothenic acid but 



