STRUCTURAL AND CHEMICAL ARCHITECTURE OF HOST CELLS 183 



Although the one carbon source, formaldehyde, is initially at a hydroxy- 

 methyl level, the final product is reduced to a methyl compound. It has been 

 suggested that the coenzyme, tetrahydrofolic acid, provides the hydrogen 

 atoms for this reduction. The mtermediates and mechanism of the reaction 

 have not yet been described. Fohc acid analogs are known to block the for- 

 mation of thymine, presumably in this reaction. In addition, 5-fluorouracil 

 deoxyriboside is phosphorylated in E. coli and the deoxyribotide is also a 

 potent inhibitor of this enzyme (Cohen, Flaks, and Earner, impublished 

 data), presumably accounting for the potent antitumor activity of fluorouracil 

 deoxyriboside. 



As presented in Fig. 1, a comparable hydroxymethylation occurs in virus- 

 infected E. coli in the conversion of deoxycytidylic acid to hydroxymethyl 

 deoxycytidyhc acid (Flaks and Cohen, 1957), However, in this case the reduc- 

 tion to the methyl level does not occur. The DNA of higher animals and 

 plants contains 5-methyl deoxycytidyhc acid but it is not known whether 

 this is made via an amination of thymidyUc acid or via the reduction of 

 the intermediate formed at the hydroxymethyl level. 



F. Biosynthesis of the Nucleic Acids 



1. The Structure of the Nucleic Acids 



It is beyond the scope of this discussion to provide a detailed analysis of 

 nucleic acid structure. The data on the composition and metabolism of the 

 nucleic acids have been summarized and analysed in many reviews. Of these 

 one important reference work is the two-volume treatise on "The Nucleic 

 Acids" (Chargaff and Davidson, 1955) which covers the field until 1954. 

 Nevertheless it will be useful to present a very brief survey of present views 

 of the polymeric nature of the naturally occurring nucleic acids, to provide 

 a suitable backdrop for the current efforts at biosynthesis. 



It is now recognized that in cells both RNA and DNA represent hetero- 

 geneous mixtures of polynucleotide polymers of considerable size. The hetero- 

 geneity of nucleic acid has been estabhshed in a variety of ways. Thus, a 

 sample of DNA or UNA isolated from cells may display physical hetero- 

 geneity under conditions of sedimentation in the analytical ultracentrifuge 

 or may be separated in chemically and physically distinct fractions by 

 column chromatography (Bendich et at., 1953; Chargaff e^ al., 1953; Bradley 

 and Rich, 1956; Miura and Suzuki, 1956). Metabolic heterogeneity of RNA 

 has been recognized in cells, since various rates of incorporation of isotopes 

 into RNA fractions of nuclei and cytoplasm have been observed. Although 

 a similar type of metabolic heterogeneity has been reported for DNA 

 (Bendich, 1952), this has not been supported (Osawa and Sakaki, 1957). 

 The latter workers have shown that when DNA is synthesized in rabbit 



