FORMIC ACID AND FORMATE METABOLISM 283 



hrought about the incorporation of C^ ^-formate into the inosijie-5-phosphate 

 provided ATP was present as a source of energy. It was shown that, 

 in this reaction, the ureide 2 carbon of inosme-5-phosphate behaved dif- 

 ferently from that of the ureide 8 carbon; thus, when a dialyzed liver 

 preparation was incubated with inosine-5-phosphate and C ^''-formate, 

 a rapid interchange in carbons took place in position 2, but no transfer 

 occurred in position ^.i^T.ies Moreover, the interchange was augmented 

 by CF, which is another indication of its participation m the transfer of 

 formate-carbon. 1^1 Although this discrepancy between the incorporation 

 of formate carbon in position 2, as distinguished from position 8, is very 

 definite in in vitro tests, it does not occur in the intact animal, in which 

 both carbons 2 and 8 appear to be derived from formate. It may take 

 place in the former case {in vitro) because of some special condition such 

 as a high concentration of inosuiic acid. 



However, m spite of the relatively clear-cut e^'idence that the formyl 

 rachcle participates in purine sjmthesis, the results of Totter and co- 

 workers ^^^ on chicks render the mechanism obscure. Thus, in folic acid- 

 deficient chicks, the incorporation of C^*-formate into the purines of the 

 viscera did not differ from that noted in control birds. '^^ On the other 

 hand, Drysdale et al.™ reported that, in the case of rats made folic acid- 

 deficient by the administration of a purified diet containing 2% of suc- 

 cinylsulfathiazole, much less labeled formate was present in the purines 

 of the nucleic acid in the liver than was found in control rats which had 

 previously received PGA (pteroylglutamic or folic acid). However, the 

 level of the purines of the extrahepatic tissues (kidneys, spleen, pancreas, 

 heart, testes, and intestines) of the foUc acid-deficient rats was not de- 

 pressed below those of the PGA-supplemented rats; in fact, the specific 

 acti\'ity of these purines was about three times that of the liver purines in 

 the PGA-treated animals. The results of Skipper et a/.,^" which demon- 

 strated that the incorporation of formate into the purines of the nucleic acid 

 of mice was depressed by the folic acid antagonist, aminopterin, have 

 been confirmed and extended in rats by Goldthwait and Bendich."^ 

 Although these divergent results are somewhat confusing, the discrepancy^ 

 may ha\'e been related to variations in the extent of deficiency of folic 



'^' J. M. Buchanan, Abstracts Am. Chem. Soc, 119th Meeting, (Boston, Mass., April, 

 1951), p. 136-146. 



i«« M. P. Schulman and J. M. Buchanan, Federation Proc, 10, 244-245 (1951). 



1" J. R. Totter, E. Volkin, and C. E. Carter, J. A/n. Chem. Soc, 73, 1521-1522 (1951). 



"0 G. R. Drvsdale, G. W. E. Plaut, and H. A. Lardy, J. Biol. Chem., 193, 533-538 

 (1951). 



"' D. A. Goldthwait and A. Bendich, Federation Proc, 10, 190 (1951). 



