156 PTEROYLGLUTAMIC ACID 



of the syndrome by PGA iii the presence of the antagonist was accompanied 

 by temporarily overcompensatory increases in total white blood cell and 

 granulocyte counts. 



This antagonist has produced symptoms of PGA deficiency in chicks, 

 mice/^ , 80 pigg^si and dogs.^- The dog does not develop deficiency symptoms 

 on a purified diet devoid of PGA even when a sulfonamide is added.^'^ The 

 deficiency syndrome which develops with the antagonist consists of loss in 

 appetite, skin changes, uticarious dermatitis, ulceration of bony prom- 

 inences, mild macrocytic anemia, and slight leucopenia. These symptoms 

 develop much more slowly than those in the rat or chick, and no diarrhea 

 or gingivitis occurs, which is characteristic of the antagonist-induced syn- 

 drome in the rat. Complete and rapid reversal of the deficiency disease is 

 produced by feeding of PGA with the continued feeding of the antagonist. 



The effects of "x methyl PGA" in affecting the action of the sex hormones 

 have already been described. 



Shive et al}^ found thymidine to be more effective than PGA in reversing 

 the action of "x methyl PGA" for Leuconostoc mesenteroides. Thymine is 

 inactive. 



b. 9- and 10- Methyl PGA derivatives 



The biological effects of a series of methyl derivatives of PGA are shown 

 in Table VII. It should be noted that the inhibition indices reported for 

 9-methyl PGA and for 9 , 10-dimethyl PGA are lower than those reported 

 elsewhere.''^ It should be borne in mind that these values are not absolute 

 but will vary from one experiment to another, depending on the time of 

 incubation, etc. Of special interest is the fact that 10-methyl PGA, which 

 is a very potent antagonist for S. faecalis, has slight pro-PGA activity for 

 chicks. The 9-methyl derivative is an antagonist for chicks and can be 

 completely reversed by PGA. The inhibitory effect of 4-amino PGA and the 

 9- and 10-methyl derivatives of 4-amino PGA on chicks is only partially 

 reversed by PGA over a narrow range of concentration. The inhibition 

 ratios of these compounds tend to decrease with increasing concentration, 



78 A. L. Franklin, E. L. R. Stokstad, T. H. Jukes, Proc. Soc. Exptl. Biol. Med. 65, 

 368 (1947). 



80 D. R. Weir, R. W. Heinle, and A. D. Welch, Proc. Soc. Exptl. Biol. Med. 69, 211 

 (1948). 



81 A. D. Welch, R. W. Heinle, G. Sharpe, W. L. George, and M. Epstein, Proc. Soc. 

 Exptl. Biol. Med. 65, 364 (1947). 



82 A. L. Franklin, T. H. Jukes, E. L. R. Stokstad, and M. Belt, Federation Proc. 8, 

 199 (1949). 



83 L. Michaud, A. R. Maass, W. R. Ruegamer, and C. A. Elvehjem, Proc. Soc. Exptl. 

 Biol. Med. 56, 148 (1944). 



8* W. Shive, R. E. Eakin, W. M. Harding, J. M. Ravel, and J. E. Sutherland, J. Am. 

 Chem. Soc. 70, 2299 (1948). 



