BIOSYNTHESIS OF NUCLEOSIDES AND NUCLEOTIDES 335 



o o 



H II 

 C^ c 

 HN^^C N H,N^ ^C N 



(a) I II II + CoF »■ II II + Formyl-CoF 



Ribose-P04 Ribose-PO« 



(b) Formyl-CoF + HC'^OOH »► C'*-Formyl-CoF + HCOOH 



n II 



HjN"^ ^C N ,4 HN^ ^C N 



(c) II II + C-- Formyl-CoF *■ I || || + CoF 



/C\ .CH HCi* Xv^ .CH 



Ribose-PO« Ribose-PO* 



Fig. 8. Possible reactions of formate and inosinic acid.^^ CoF (coenzyme F) indi- 

 cates 5,6,7,8-tetrahydrofolic acid. Formyl-CoF (citrovorum factor) indicates N-5- 

 formyl-5,6,7,8-tetrahydrofolic acid. (See also Fig. 6 in Chapter 23.) 



2. Citrovorum Factor (Leucovorin, Folinic Acid SF, Coenzyme F) 



Citrovorum factor is named for its growth-promoting activity for Leu- 

 conostoc citrovorum. It is a derivative of folic acid, namely, A''-5-formyl- 

 5 , 6 , 7 , 8-tetrahydropteroylglutamic acid.'^*^^^ A role of the citrovorum fac- 

 tor in purine synthesis was suggested by Shive,^^- and his hypothesis was 

 put to a test by Buchanan and Schulman^' in the system of inosinic acid 

 formation from 4-amino-5-imidazolecarboxamide ribotide. Both folic acid 

 and citrovorum factor were found to activate the incorporation of radio- 

 active formate into inosinic acid by exchange with carbon atom 2 of the 

 base in presence of pigeon liver extracts. Citrovorum factor surpassed folic 

 acid greatly in its activating effect, but the amounts used (5 to 45 Mg-/nil.) 

 are rather high.^^ya Three- to fourfold increase in the rate of formyl incor- 

 poration was achieved. Buchanan and Schulman^* represent the reaction 

 as shown in Fig. 8. 



Besides carbon atom 2, purine carbon 8 and the 5-methyl group of thy- 

 mine may be derived from formic acid"'^^*-^^*"'^ and a similar formulation as 

 given above appears possible. Other effects may concern one-carbon trans- 

 fers in the synthesis of aliphatic purine and pyrimidine precursors, but these 



'" A. Pohland, E. H. Flynn, R. A. Jones, and W. Shive, J. Am. Chem. Soc. 73, 3247 



(1951). 

 1" H. P. Broquist, M. J. Fahrenbach, J. A. Brockman, Jr., E. L. R. Stokstad, and 



T. H. Jukes, J. Am. Chem. Soc. 73, 3535 (1951). 

 1"^ G. R. Greenberg, Federation Proc. 13, 221 (1954). 



128 J. M. Buchanan, J. C. Sonne, and A. M. Delluva, J. Biol. Chem. 173, 81 (1948). 

 '28» D. A. Goldthwait and A. Bendich, J. Biol. Chem. 196, 841 (1952). 

 128b p. Berg, J. Biol. Chem. 205, 145 (1954). 



