ANALOGUES 



both, whilst one compound increased weight but reduced haemoglobin 

 formation (page 518). 



Folic Acid, p-Axninobenzoic Acid and Sulphonamides 



The discovery that ^-aminobenzoic acid was present in the folic 

 acid molecule directed attention to the relationship between the growth- 

 promoting activities of the two substances and of compounds 

 intermediate between them. ^-Aminobenzoic acid stimulated the 

 growth of organisms for which pteroylglutamic acid was not an 

 essential growth factor (see page 556), and vice versa. The matter was 

 of especial interest in view of the fact that sulphonamides owe their 

 antibacterial properties to competition with ^-aminobenzoic acid for 

 an enzyme system essential for the life of the bacterial cell (page 546). 



The first attempt to determine the relative functions of _/)-amino- 

 benzoic acid and pteroylglutamic acid in the nutrition of micro- 

 organisms was made by J. O. Lampen and M. J. Jones /^ who found 

 that L. helveticus and S. faecalis R were not inhibited by sulphadiazine 

 in a basal medium free from ;/)-aminobenzoic acid when either pteroyl- 

 glutamic acid or thymine was added. The antagonism between 

 sulphadiazine and ;/)-aminobenzoyl-L-glutamic acid was competitive, 

 whereas that between sulphadiazine and folic acid or thymine was not. 

 These observations led the authors to suggest that sulphonamides 

 owed their antibacterial action to their ability to interfere with the 

 sjmthesis of pteroylglutamic acid from ;/)-aminobenzoic acid. 



Similar results were obtained with sulphanilamide, sulphathiazole 

 and sulphapyridine. Inhibition of sulphonamide activity also occurred 

 with L. arabinosus, but not with E. coli, S. aureus or D. pneumoniae. 

 Pteroylglutamic acid would therefore be expected to interfere with 

 sulphonamide therapy in relatively few infections. 



A mutant of E. coli that required ;/)-aminobenzoic acid for growth 

 was not stimulated by folic acid or by thymine alone, ^* but a mixture 

 of thymine, purines and amino acids was able to replace p-djoamo- 

 benzoic acid for this strain. 



The Ralston strain of S. faecalis was found to synthesise pteroyl- 

 glutamic acid, although at a sub-optimal rate.^^ In this instance, 

 inhibition by sulphonamides was antagonised non-competitively by 

 pteroylglutamic acid, pteroyltriglutamic acid and thymine. The 

 amoimt required for sulphonamide antagonism was approximately the 

 same as that required by S. faecalis R for growth. Similarly, strains 

 of Enterococcus that could not synthesise pteroylglutamic acid, but 

 required the addition of the preformed factor, were insensitive to 

 sulphonamides, whereas strains that were able to synthesise the factor 

 were sensitive, except when pteroylglutamic acid was added to the 

 medium. S. faecalis R and L. helveticus, grown in presence of pteroic 



5^5 



