FORMIC ACID AiND FORMATE METABOLISM 281 



In more recent studies on the enzyme system involved in formylations, 

 Rauen and Jaenicke^^ demonstrated that foHc acid can also serve as the 

 transformylating agent. It is now recognized that folic acid (also called 

 "pteroylglutamic acid") is changed in the animal to a compound which 

 is called folmic acid. The latter compound appears in the urine after the 

 administration of folic acid. It can also be synthesized by the liver in 

 vitro. Folinic acid appears to be a reduced form of folic acid, and it is 

 identical with LCF (or CF). 



The enzyme system which mediates the reaction was prepared from liver 

 homogenates. Mutton liver was found to be the most active source, 

 followed in order by that of the pig, ox, and calf; dog liver was inactive. 

 Enzymatic formylation of folic acid depends upon an intact respiration, 

 and hence it is inhibited by cyanide, azide, and iodoacetate. ATP in- 

 creases the rate of reaction, while DPN is without effect. Serine and 

 histidine were fomid to be the most active formyl donors; uric acid, 

 acetate, formate, thymine, uracil, and hypoxanthine were less active in 

 this respect. Gtycine had only a slight acti\'ity, and methionine, choline, 

 and betaine were completely inacti^-e. 



The (N) (12) formyl-folic acid was shoAvn by Rauen and Jaenicke'®" 

 to be relatively stable under aerobic conditions, even in the presence of 

 formyl acceptors. On the other hand, the transfer of the formyl group 

 occurred slowly under anaerobic conditions, in the absence of acceptors, 

 while the reaction proceeded rapidly when acceptors were present. Glycine, 

 pyruvic acid, and uracil were the best acceptors. ATP and DPN were 

 like^^^se required for the completion of the transformylation. Folic acid 

 antagonists inhibited the synthesizing but not the decomposition reactions. 

 Since both the energy of respiration and ATP are required for the contin- 

 uance of the reaction, it is suggested that this formyl group should be 

 referred to as "activated formate." 



Formate, presumably in the active form, is now kno\\Ti to be involved 

 in many synthetic reactions. Presumably, CF may function as a donor 

 of the formyl group, while one may also postulate that 5,6,7,8-tetrahydro- 

 pteroylglutamic acid might act as an acceptor of formyl groups which 

 have been set free. The reactions may be somewhat complex, and they 

 may require the assistance of cof actors other than those obtained from 

 folic acid. Welch and NichoP^^ illustrated the several reactions involving 

 the formation or utilization of formic acid, in the diagram presented below: 



i«» H. M. Rauen and L. Jaenicke, Z. physiol. Chem., 293, 46-47 (1953). 



1" A. D. Welch and C. A. Nichol, Ann. Rev. Biochem., 21, 633-686 (1952). 



