IV 



NUCLEOTIDE SYNTHESIS 



93 



HC N 



NHj Ribose-5'-P 

 (AIR) 



COj 

 ATP 



asportic 



COOH 

 I 



CH 

 I 



CH-COOH 

 I 

 HN-C=0 

 I 

 C — N 



C — NH ^TP 



II I , ; 



NH Ribose-5-P 

 (FGAM) 



(FGAR) 



-fumaric 



o 



II 



NH,-C 

 I 

 ^ C — N 



CH 



N-C— N^ 



2 Ribose-5-P 



5-Amino-4 imidazole 

 <N- Succinylocarboxamide) 

 ribotide 



Ribose-5'-P 

 Adenylosuccinate 



GTP 

 aspartate 



c=o 



C— N 



%. 



NHj-C — tjJ 



Ribose-5'-P 

 (AICAR) 

 Aminoimidazole- 

 carboxamide 

 ribotide 



II '^^ 



C — N-^ 



Ribose-5'-P 

 Inosinic 

 (IMP) 



Fig. 44. Pathway of de novo purine nucleotide synthesis. 



-^"^C, when the enzyme system is supplemented with bicarbonate, formate, gluta- 

 mine, aspartate, and 3-phosphoglycerate. Non-labelled glycine does not inhibit 

 this process. With FGAR, labelled with ^"^C on the formate group, inosinic 

 acid-8-^'*C is obtained. The [^-carbon of serine can also function as a precursor of 

 the formyl group of FGAR (Warren and Flaks, 1956). High levels ofglutamine 

 reverse the inhibitory effect of azaserine on de novo synthesis of inosinic acid. 

 Tetrahydrofolic acid (THFA) or the citrovorum factor is required for the synthesis 

 of FGAR from its precursors (Goldthwait et al., 1954, 1956). 



Using enzymes from pigeon liver extracts fractionated with ethanol, it was 

 shown that FGAR reacts with glutamine to yield an arylamine which on incuba- 



Literalurc p. 124 



