462 R. E. HANDSCHUMACHER AND A. D. WELCH 



It was shown several years ago that the incorporation of formate-carbon 

 into positions 2 and 8 of nucleic acid purines occurs to an equal extent in 

 vivo, but, as has been noted, 14 it is not clear why this is so when a very ac- 

 tive inosinic acid transformylase system, dependent upon FH4 , operates 

 effectively to exchange with formate the carbon is position 2, at least in a 

 cell-free system obtained from pigeon liver. Similarly, the accumulation, in 

 many biological systems inhibited by folic acid-antagonists, of aminoimida- 

 zolecarboxamide (or derivatives of it), suggests that the earlier formylation 

 of the ribonucleotide of glycinamide is far from completely inhibited, under 

 conditions which lead to a profound interference with the formylation of 

 the imidazole derivative. This difference in the apparent inhibitory effect 

 of amethopterin may be a reflection of different affinities of the two trans- 

 formylases for FH 4 (the coenzyme in both reactions). 



In the enzymic degradation of purines, at least by Clostridium cylindro- 

 sporum, an additional FH 4 -dependent reaction occurs: the breakdown of 

 formiminoglycine (derived by opening of the ring of 4-imidazolone arising 

 from xanthine). This sequence of reactions, utilized by this organism as its 

 only source of energy, also has been exploited for the determination of aden- 

 osine triphosphate (ATP), formate, and FH 4 , and is very useful in the 

 detection of a state of folic acid-deficiency. 52 The key reactions are: 



Forminoglycine + FH 4 ;=± glycine + ^ 5 FH 4 (formimino transferase) (1) 



^ 6 FH 4 ;=i/ 6 - 10 FH 4 + NH 3 (cyclodeamimase) (2) 



/ 5 - 10 FH 4 + ADP + Pi ^ formate + FH 4 + ATP (tetrahydrofolic formylase) (3) 



Although only indirectly concerned with nucleic acid metabolism, men- 

 tion should be made of recent advances in our knowledge of the catabolism 

 of L-histidine. This is because of the involvement of a FH 4 -dependent trans- 

 fer of the formimino group from the intermediate formiminoglutamic acid 

 (in a manner similar to that discussed above) , and the important analytical 

 applications of these reactions in the detection of a state of folic acid-de- 

 ficiency, in which formiminoglutamic acid appears in the urine, particularly 

 following the administration of L-histidine. A large volume of literature 

 concerning this field exists to which only a few key references can be given 

 here. 53 " 56 



60 L. D. Wright and A. .D. Welch, Science 98, 179 (1943). 



61 A. D. Welch, E. M. Nelson, and M. F. Wilson, Federation Proc. 8, 346 (1949). 



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

 Rabinowitz, Abstr., Gordon Research Conf., New London, New Hampshire, p. 83 

 (1957). 



53 H. Bakerman, M. Silverman, and F. S. Daft, J. Biol. Chem. 188, 177 (1951). 



54 B. Borek and H. Waelsch, J. Biol. Chem. 205, 459 (1953). 



56 J. C. Rabinowitz and H. Tabor, J. Biol. Chem. 233, 252 (1958). 



56 H. H. Hiatt, M. Goldstein, and H. Tabor, J. Clin. Invest. 37, 829 (1958). 



