614 G. SCHMIDT 



VIII. Enzymes Involving the Opening of the Purine Ring 



Up to the discovery of 4-amino-5-imidazolecarboxamide"^^^'' and its 

 role in the formation of the purine ring, the only enzyme known to catalyze 

 the biological degradation of the purine ring was uricase. Whereas the latter 

 enzyme reaction is most likely irreversible in the sense that no evidence 

 exists for the participation of allantoin and its intermediary precursors in 

 purine biosynthesis, the formation of 4-amino-5-imidazolecarboxamide com- 

 pounds has been shown to be an important step in the biological formation 

 of the purine ring. The study of the enzymes involved in the metabolism of 

 4-amino-5-imidazolecarboxamide is still in the early stages and the role of 

 this compound in purine biosynthesis is discussed in Chapter 23, but, in 

 anticipation of the increasing importance of this field, a brief review of the 

 available observations is included in this chapter. 



In contrast to the action of uricase, the enzyme reactions involving the 

 4-amino-5-imidazolecarboxamide group occur exclusively on nucleotide 

 compounds. 



1. Inosinic Acid Transformylase 



An enzyme fraction obtained from pigeon liver extracts by fractional 

 precipitation with alcohol catalyzes the reversible-^^J ••= transformation of 

 inosinic acid to 4-amino-5-carboxamide ribotide in the presence of certain 

 formyl acceptors. The yield of the reaction product is strongly dependent 

 on the concentration of inosinic acid. The reaction requires ATP and mag- 

 nesium ions.^'®'-™ It is enhanced by glycine (but not by other amino acids 

 such as L-methionine, L-alanine, L-serine, L-leucine, and sarcosine) and by 

 leucovorin. The reaction is strongly stimulated by copper ions at 1 X 10"'' M. 



The enzyme is completely inhibited by cyanide or versene. 



Assay. The action of inosinic transformylase can be followed by the de- 

 termination of the quantities of the arylamine formed by means of the 

 diazo reaction of Bratton and Marshall.^^^" 



2. Uricase 



History. The earliest observations on the power of mammalian tissues to 

 destroy uric acid date back to Ascoli-" and Wiener.^^^ Schittenhelm^^^ came 



"6i W. Shive, W. W. Ackermann, M. Gordon, M. E. Getzendaner, and R. E. Eakin, 



J. Am. Chem. Soc. 69, 725 (1947). 

 236i J. M. Buchanan and M. P. Schulman, J. Biol. Chem. 202, 241 (1953). 

 236k J. G. Flaks and J. M. Buchanan, J. Am. Chem. Soc. 76, 2275 (1954). 

 2361 G. R. Greenberg, Federation Proc. 13, 221 (1954). 

 236m Q R Greenberg, Federation Proc. 13, (1954), in press. 

 2'6n A. C. Bratton and E. K. Marshall, Jr., /. Biol. Cherti. 128, 537 (1939). 



237 G. Ascoli, Pflilgers Arch. ges. Physiol. 72, 340 (1898). 



238 W. Wiener, Z. physiol. Chem. 43, 532 (1904). 



239 J. A. Schittenhelm, Z. physiol. Chem. 45, 121 (1905). 



