124 H. GOBIND KHORANA 



III. Enzymic Synthesis of Ribopolynucleotides 29 



1. Introduction 



Mechanisms for the enzymic synthesis of mononucleotides are discussed 

 in Chapters 35 and 36. Progress in the understanding of the enzymic path- 

 ways for the synthesis of polynucleotides from mononucleotide precursors 

 has been striking during the last five or six years and there has been a 

 marked changed in the views on the subject since a related review (Volume 

 II, Chapter 25) was written. In vitro studies on the incorporation of nucleo- 

 tide precursors into polynucleotides and the discoveries of the nucleoside- 

 5'-mono-, di-, and triphosphates corresponding to all of the naturally oc- 

 curring purines and pyrimidines in the acid-soluble nucleotide pools of 

 different tissues 30 heightened the supposition that nucleoside-5'-di- or tri- 

 phosphates might be the biological precursors of polynucleotides. Discrete 

 enzymic reactions utilizing nucleoside-5'-polyphosphates as substrates have 

 indeed been discovered in the synthesis of both series, the ribo- and deoxy- 

 ribopolynucleotides. It should be emphasized that in the following, the 

 review of this progress is limited to the in vitro enzymic studies of the for- 

 mation of polynucleotides and, in particular, to those reactions where the 

 nature of the starting materials and products is known with reasonable 

 certainty. 



2. rlbonucleoside-5'-dlphosphates as precursors 

 of Ribopolynucleotides 



The discovery of an enzyme which catalyzes the synthesis of high molecu- 

 lar weight ribopolynucleotides from ribonucleoside-5 '-diphosphates with the 

 release of inorganic phosphate was made by Grunberg-Manago and Ochoa 31 

 in 1955. The reaction in so far as it may be simply represented by Eq. (1), 

 is reminiscent of the reaction of polysaccharide phosphorylase and the en- 

 zyme was therefore called polynucleotide phosphorylase. The enzyme was 

 first isolated from the microorganism Azotobacter vinelandii, 31, 32 but soon 

 similar enzymes were described by Littauer and Romberg 33 in Escherichia 

 coli and by Beers 34, 35 in Mircococcus lysodeikticus. 



29 In the following sections some additional abbreviations, which are commonly ac- 

 cepted, are used. These are: ribonucleic acid, RNA; deoxyribonucleic acid, DNA; 

 adenosine-5' diphosphate, ADP; guanosine-5' diphosphate, GDP; cytidine-5' 

 diphosphate, CDP; uridine-5' diphosphate, UDP; uridine-5' triphosphate, UTP; 

 guanosine-5' triphosphate, GTP; the triphosphates of the corresponding deoxyri- 

 bonucleosides are prefixed by the letter 'd'; inorganic pyrophosphate, PP. 



30 H. Schmitz, R. B. Hurlbert, and V. R. Potter, J. Biol. Chem. 209, 41 (1954). 



31 M. Grunberg-Manago and S. Ochoa, J. Am. Chem. Soc. 77, 3165 (1955). 



32 M. Grunberg-Manago, P. J. Ortiz, and S. Ochoa, Biochim. et Biophys. Acta 20, 269 

 (1956). 



33 U. Z. Littauer and A. Romberg, J. Biol. Chem. 226, 1077 (1957). 



