176 S. S. COHEN 



contents when the protein has been synthesized in an organism incubated 

 with a radioactive amino acid. This problem has been discussed in detail by 

 Steinberg et al. (1956). Although in some cases nonuniform labeling has been 

 observed, suggesting the possible stepwise formation of intermediate pep- 

 tides, it is not yet known how long it takes to make a protein molecule 

 (Dalgleish, 1957). Thus, it is conceivable that nonuniform labeling may occur 

 as a result of the changes m the free amnio acid pool, if it takes an appreci- 

 able time to produce a polyj^eptide chain, even when this is being elaborated 

 at a single fixed template by a so-called zipper action. 



Considerable lags have been observed in the elaboration and appearance 

 of some proteins, such as serum albumin (Peters, 1953), suggesting the exist- 

 ence of many intermediates. However, other workers have found very short 

 periods of this kind, as for ferritin production in Hver (Loftfield, 1956). 

 Indeed, Peters, T. (1957) has recently reported that durmg the lag, serum 

 albumin-like proteins may be detected bound to cytoplasmic particles, from 

 which they are then presumably released. Although the problem of the time 

 of synthesis of a protein molecule has not yet been satisfactorily solved 

 (Craddock and Dalgleish, 1957), it seems possible that it is indeed very short. 



Before turning to questions of the specificity of peptide organization, pre- 

 sumably as directed by templates, we shall first consider existing data on 

 nucleic acid formation. 



E. The Biosynthesis of Nucleic Acid Intermediates 



In the intermediary metabolism of protein biosynthesis it was seen that the 

 focal building blocks were the amino acids. The formation of each of these 

 may involve a long and characteristic sequence of reactions, leading to the 

 existenceof several hundred mtermediatesfor this general area of metaboHsm. 

 In contrast to this situation, the intermediary metabolism of the nucleic acids 

 has many fewer independent reaction sequences. These may be grouped, as 

 indicated earher, into scavengmg reactions permitting the recovery of ingested 

 nucleic acid and reactions of de novo biosynthesis (Kornberg, 1957a). 



1. Scavenging Reactions 



In the former category are reactions which, for the most part, have been 

 indicated earlier: (a) hnkage of free bases to ribose-1 -phosphate or deoxyri- 

 bose-1-phosphate to form a ribo- or deoxyribonucleoside, respectively; (b) 

 the phosphorylation of the nucleoside to nucleotide; (c) the linkage of free 

 base (purine or pyrimidine) to 1-pyropliosphoryl ribose-5-phosphate to 

 form a purine or pyrimidine ribonucleotide. In addition, transglycosidations 

 via nonphosphorylytic reactions permit formation of new nucleosides from 

 bases and nucleosides. In all of these reactions, the organism is called upon 



