318 JOHN M. BUCHANAN 



formyltetrahydrofolic acid. When cyclohydrolase is eliminated, however, 

 the reaction becomes specific for the iV 10 -formyl derivative. 



The two transformylase reactions of purine biosynthesis may be coupled 

 with each other in the direction indicated in Eq. (13). 60 This composite 



Inosinic acid + glycinamide ribonucleotide + H 2 — > 



5-amino-4-imidazolecarboxamide ribonucleotide (13) 



+ formylglycinamide ribonucleotide 



reaction requires the participation of inosinicase, the carboxamide ribo- 

 nucleotide transformylase, cyclohydrolase, and glycinamide ribonucleotide 

 transformylase in the order named. Equation (13) is essentially irreversible 

 because of the irreversibility of the last reaction of the series, the formyla- 

 tion of glycinamide ribonucleotide. 



IV. Enzymic Synthesis of Formyltetrahydrofolic Acid Compounds 



The enzymic formation of the formylated derivatives of tetrahydrofolic 

 acid has now been studied extensively. A 10 -Formyltetrahydrofolic may be 

 formed directly by the coupling of formic acid and tetrahydrofolic acid in 

 the presence of ATP according to Eq. (14). 58 ' 61 A 5 ,A/ 10 -Anhydroformyl- 



Formic acid + FH 4 + ATP «=± A'">-formyl-FH 4 + ADP + orthophosphate (14) 



tetrahydrofolic acid, which is also referred to as A^A^-methenyltetra- 

 hydrofolic acid, may be derived from serine 62 " 67 by reactions shown in Fig. 

 7 (see also footnote 11 in Chapter 39). 68 " 70 In certain bacteria which ca- 

 tabolize purines as a source of energy, A^ A 10 -anhydroformyltetrahydrofolic 

 acid may be formed from formiminoglycine by reactions included in Fig. 7. 

 Formiminotetrahydrofolic acid may also be formed from formiminoglutamic 

 acid which is produced in the catabolism of histidine in mammalian liver. 71,72 

 A third form of formyltetrahydrofolic acid, the N 5 derivative, has been 



61 J. C. Rabinowitz and W. E. Pricer, Jr., Federation Proc. 17, 293 (1958). 



62 N. Alexander and D. M. Greenberg, J. Biol. Chem. 214, 821 (1955). 



63 N. Alexander and D. M. Greenberg, J. Biol. Chem. 220, 775 (1956). 



64 R. L. Kisliuk, Federation Proc. 15, 289 (1956). 



65 L. Jaenicke, Federation Proc. 15, 281 (1956). 



66 G. R. Greenberg and L. Jaenicke, in "The Chemistry and Biology of the Purines" 

 (G. E. W. Wolstenholme and C. M. O'Connor, eds.), p. 204. Churchill, London, 

 1957. 



67 M. J. Osborn and F. M. Huennekens, Biochim. et Biophys. Acta 26, 646 (1957). 



68 J. C. Rabinowitz and W. E. Pricer, Jr., J. Am. Chem. Soc. 78, 5702 (1956). 



69 J. C. Rabinowitz and W. E. Pricer, Jr., J. Am. Chem. Soc. 78, 1513 (1956). 



70 J. C. Rabinowitz and W. E. Pricer, Jr., J. Am. Chem. Soc. 78, 4176 (1956). 



71 A. Miller and H. Waelsch, Arch. Biochem. Biophys. 63, 263 (1956). 



72 H. Tabor and J. C. Rabinowitz, J. Am. Chem. Soc. 78, 5705 (1956). 



