36. BIOSYNTHESIS OF PYRIMIDINE NUCLEOTIDES 335 



The biosynthesis of cytidine nucleotide coenzymes has been reviewed re- 

 cently by Baddiley and Buchanan 76 and will not be discussed here. 



2. Biosynthesis of Deoxycytidine-5'-mono-, di-, 

 and triphosphates 



Deoxycytidine nucleotides have been isolated from the acid-soluble frac- 

 tion of thymus. 92 ' 93 Deoxycytidine-5'-phosphate (dCMP) can be phos- 

 phorylated by ATP in the presence of the cytidine monophosphate kinase 

 described by Maley 79 and the product further phosphorylated to the corre- 

 sponding triphosphate (dCTP) by a nucleoside diphosphate kinase. Leh- 

 man et al. Si have purified similar kinases from E. coli B. The 5'-di- and tri- 

 phosphates of deoxycytidine (and thymidine) have been isolated following 

 the ATP-linked phosphorylation of the corresponding deoxynucleoside-5'- 

 phosphate by rat liver homogenates and by a high-speed supernatant frac- 

 tion of regenerating rat liver. 95 



The de novo synthesis of deoxycytidine nucleotides probably involves a 

 pathway of the following type: 



-> UMP -^ UDP -> UTP -> CTP -» ? -> dCMP 



The available evidence indicates that dCTP is not formed by animation of 

 deoxyuridine-5'-triphosphate by analogy with the UTP/CTP conversion. 

 Thus C 14 -deoxyuridine is an effective precursor of DNA-thymine but not 

 of DNA-cytosine or RNA-pyrimidines of regenerating liver, 96 intestinal 

 mucosa, 96 minced chicken embryo, 97 and suspensions of rabbit and chicken 

 bone marrow cells. 97 Further, Friedkin and Romberg 98 have shown in a 

 study of the 5'-deoxynucleotide kinase activity of E. coli extracts that no 

 activity with respect to deoxyuridine-5'-phosphate (dUMP) could be de- 

 tected. 



Implicit in the proposed pathway of de novo deoxycytidine nucleotide 

 formation is the conversion of a ribose residue to a 2-deoxyribose residue. 

 The problem of deoxyribose synthesis will be discussed later but it may be 

 noted that a considerable body of evidence exists pointing to a ribose to de- 

 oxyribose conversion at the level of a nucleoside or nucleotide without the 



92 R. L. Potter and S. Schlesinger, J. Am. Chem. Soc. 77, 6714 (1955). 



93 R. L. Potter, S. Schlesinger, V. Buettner-Janusch, and L. Thompson, J. Biol. 

 Chem. 226, 381 (1957). 



94 I. R. Lehman, M. J. Bessman, E. S. Simms, and A. Romberg, J. Biol. Chem. 233, 

 163 (1958). 



95 E. S. Canellakis and R. Mantsavinos, Biochim. et Biophys. Acta 27, 643 (1958). 



96 P. Reichard, Acta Chem. Scand. 9, 1275 (1955). 



97 M. Friedkin and D. Roberts, J. Biol. Chem. 220, 653 (1956). 



98 M. Friedkin and A. Romberg, in "The Chemical Basis of Heredity" (W. D. Mc- 

 Ehoy and B. Glass, eds.), p. 609. Johns Hopkins Press, Baltimore, 1957. 



