35. BIOSYNTHESIS OF PURINE NUCLEOTIDES 321 



acid has been studied by three groups of investigators. 80-84 Enzymes have 

 been isolated from pigeon liver, rabbit bone marrow, and calf thymus which 

 are capable of effecting the amination of xanthylic acid to guanylic acid 



Xanthylic acid + glutamine -f- ATP + H 2 «=± 



(18) 

 guanylic acid + glutamic acid + AMP + pyrophosphate 



according to Eq. (18). An enzyme obtained from Aerobacter aerogenes, 

 xanthosine-5'-phosphate aminase utilizes ammonia as the nitrogen donor 

 rather than glutamine in a similar amination reaction. The enzyme isolated 

 from animal sources may also utilize ammonium ions as a nitrogen donor 

 but much less effectively than the preferred substrate, glutamine. 



Isotopic experiments indicate that like other nitrogen transfer reactions 

 involving glutamine Eq. (18) is essentially irreversible. It differs from the 

 reaction of formylglycinamidine ribonucleotide synthesis in that the nu- 

 cleoside phosphate products of the reaction are AMP and pyrophosphate 

 rather than ADP and orthophosphate. 18 -transfer experiments show that 

 the nucleophilic displacement on ATP must occur at the innermost phos- 

 phorus atom rather than at the terminal one. Azaserine will inhibit the 

 synthesis of guanylic acid from xanthylic acid. The inhibition constant for 

 this reaction is much higher than it is for the amination of formylglycin- 

 amide ribonucleotide. 



VII. Summary 



The synthesis of inosinic acid from elementary precursors can be con- 

 sidered as taking place by coupling of Eqs. (19) and (20). In these reactions 



2NH 4 + + 2HCOO" + HCOr + glycine + aspartate + ribose-5-phosphate -» 



(19) 

 inosinic acid + fumarate + 9H>0 



9ATP + 9H 2 -> 8ADP + 8HPOr + AMP + HPjOr + 9H + (20) 



the assumption is made that the two ammonium ions are being incorpo- 

 rated first into the actual nitrogen donor, glutamine, by reaction with glu- 

 tamic acid and ATP. At least in theory aspartate could be derived from 

 fumarate and NH 4 + according to Eq. (21) 85 so that Eq. (19) may be reduced 



Fumarate + NH 4 + — » aspartate (21) 



Glycine + ribose-5-phosphate + 3NH 4 + + HCCV + 2HCOQ- -» 



(22) 

 inosinic acid + 9H2O 



80 R. Abrams and M. Bentley, Arch. Biochem. Biophys. 79, 91 (1959). 



81 U. Lagerkvist, J. Biol. Chem. 233, 138 (1958). 



82 U. Lagerkvist, J. Biol. Chem. 233, 143 (1958). 



83 B. Magasanik, H. S. Moyed, and L. B. Gehring, J. Biol. Chem. 226, 339 (1957). 



84 H. S. Moyed and B. Magasanik, J. Biol. Chem. 226, 351 (1957). 



85 V. R. Williams and R. T. Mclntyre, J. Biol. Chem. 217, 467 (1955). 



