350 



CELLS, TISSUES, AND ORGANISMS 



Glycine or 

 Glutamate 



5-CHNHFAH4 



Purines — ►FIG 

 Histidine-^FIGI 



Aminoptenn 



PABA + 

 pteridine+. 

 qlutomofe N4 



Serine // FAICAR AICAR 



IO-CHOFAH4 



Thymidylote 



Deoxyuridylote 



Figure 11. Biochemical transformations of folic-acid coenzymes, showing 

 action of aminopterin in preventing regeneration of tetrahydrofolic acid 

 (FAHJ. 



glycinamide ribotide; AICAR = aminoimidazole carboxamide ribotide; 

 FAICAR = formylaminoimidazole carboxamide ribotide; PABA = 

 para-aminobenzoic acid. 



The finding at the enzymatic level that aminopterin combines, ap- 

 parently irreversibly, with dihydrofolic reductase serves to clear up 

 some earlier observations on bacterial growth. It was noted that ami- 

 nopterin inhibits the growth of E. coli, and that this inhibition is re- 

 versed by thymidine (Franklin et al, 1949). This may indicate that 

 E. coli cannot synthesize tetrahydrofolic acid rapidly enough to renew 

 the supply that is "trapped" by aminopterin when tetrahydrofolic acid 

 is dehydrogenated to form dihydrofolic acid during the synthesis of 

 thymidine. If preformed thymidine is supplied, the thymidylate syn- 

 thetase reaction may be slowed down, and the de novo synthesis of 

 tetrahydrofolic acid by E. coli may then be sufficiently rapid to supply 

 the requirement for various reactions, such as the formation of purines. 



It was observed with Leuconostoc citrovorum that growth on a 



