35. BIOSYNTHESIS OF PURINE NUCLEOTIDES 309 



Because of the central location in the purine ring of the carbon and 

 nitrogen atoms derived from glycine, it was considered likely that this 

 precursor would participate in one of the early reactions of purine biosyn- 

 thesis. This indeed proved to be the case. Goldthwait et a/. 26 found that two 

 phosphoribosyl derivatives of glycinamide accumulated when glycine, 

 glutamine, formate, ribose-5-phosphate, and ATP were incubated with 

 crude extracts of pigeon liver. The two compounds 26 " 29 have been isolated, 

 purified, and demonstrated to have the structures shown in Fig. 4. These 

 compounds have been given the trivial names, glycinamide ribonucleotide 

 and formylglycinamide ribonucleotide. In the absence of formate or of 

 tetrahydrofolic acid or its formyl derivative, formylglycinamide ribonucleo- 

 tide is not formed. 



Ribose-5-phosphate 4- ATP — > 5-phosphoribosyl-l-pyrophosphate + AMP (1) 



The discovery that phosphoribosyl derivatives were involved in purine 

 biosynthesis had initiated a series of investigations to determine the na- 

 ture of the reaction and the intermediates involved in the synthesis of these 

 compounds. Toward this end the synthesis of inosinic acid from hypoxan- 

 thine, ribose-5-phosphate, and ATP was studied by Williams and Bu- 

 chanan, 30 and by Korn et al. u • 32 From this model system a new mechanism 

 for the synthesis of nucleotides from bases was discovered which involved 

 the reaction of ribose-5-phosphate and ATP [Eq. (1)] to yield a new 

 ribosyl intermediate first identified by Romberg and his associates 33 as 

 5-phosphoribosyl-l -pyrophosphate. It is now known that the two terminal 

 phosphate groups of ATP are transferred as a unit to ribose-5-phosphate 

 in the presence of the enzyme 5-phosphoribose pyrophosphokinase. 34 5-Phos- 

 phoribosylpyrophosphate may undergo condensation with a number of 

 bases with the liberation of inorganic pyrophosphate in the presence of a 



26 D. A. Goldthwait, R. A. Peabody, and G. R. Greenberg, J. Am. Chem. Soc. 76, 

 5258 (1954). 



27 S. C. Hartman, B. Levenberg, and J. M. Buchanan, J. Am. Chem. Soc. 77, 501 

 (1955). 



28 S. C. Hartman, B. Levenberg, and J. M. Buchanan, J. Biol. Chem. 221, 1057 (1956). 



29 R. A. Peabody, D. A. Goldthwait, and G. R. Greenberg, J. Biol. Chem. 221, 1071 

 (1956). 



30 W. J. Williams and J. M. Buchanan, J. Biol. Chem. 203, 583 (1953). 



31 E. D. Korn and J. M. Buchanan, Federation Proc. 12, 233 (1953). 



32 E. D. Korn, C. N. Remy, H. C. Wasilejko, and J. M. Buchanan, J. Biol. Chem. 

 217,875 (1955). 



33 A. Romberg, I. Lieberman, and E. S. Simms, J. Biol. Chem. 216, 389 (1955). 



34 H. G. Khorana, J. F. Fernandes, and A. Kornberg, J. Biol. Chem. 230, 941 (1958). 



