180 



S. S. COHEN 



.NHz 



I 



HCOH 



I 

 HCOH 



I 



HC 



H,C-NH, HCOOH ".C-NH ^^p H,C-NH 



^f'lr ATP CHO Glutamine | CHO 



Glycine | >■ I — 



- ^ .. ++ X.C "Folic acid" ^C. 



^9 6^ ^NH cf ^NH 



I I ' 



Ribose - PO4 Ribose - PO4 R'bose - PO4 



HN^ "^NH 



H2COPO3H2 HOOC 



5 — phosphoribosyl |_| q 



H 



O 

 II 



/C. / 



H2N N 



Ribose PO4 



Serine 

 TPN 

 "Folic acid" 



O 



H.N-'^-cA 



II >H 

 HCp C^ / 



H 



HC-N-C=0 



COOH 

 ' .N 



ATP 

 Mg++ 





Ribose PO4 



H2N' 'N H2N N 



Ribose PO4 Ribose - PO4 



H,N^ 'N 



Ribose -PO4 



NH- 

 I 



O 



II 



HN'^ ^C^ \ 

 r!^ I II /H 



^N N 

 I 

 Ribose PO4 



Inosinic acid 



^/'^N^/^^v Adenylic 



f if \h --'^ 



HC,, /C^ / 

 ^N^ N 



Ribose PO4 



OH 



I II \h ^'^^^y"^ 



1 



Ribose PO4 



(XXVIII) 



The critical role of glutamine in at least three steps of purine biosynthesis 

 suggests the potential role of glutamine analogs in blocking nucleic acid 

 biosynthesis. Of the several glutamine-requiring reactions known, one is 

 particularly sensitive to the two glutamine analogs, aza-L-serine and 6- 

 diazo-5-oxo-L-norleucine (Levenberg et at., 1957). This is the conversion of 

 formyl glycinamide ribotide to formylglycineamidine ribotide, as indicated 

 in the schema, m which the enzyme is irreversibly inactivated by the anti- 

 biotics. That azaserine can effect this inhibition has been demonstrated 

 with intact organisms, e.g., E. coli (Tomisek et al., 1956). The possible 

 activity of azaserme has not yet been adequately explored m virus-infected 

 cells; it should be noted that the growth of mammalian cells in tissue culture 

 requires glutamine, as does the production of certain viruses in such cells 

 (Eagle and Habel, 1956). 



