310 F. SCHLENK 



vestigators in this field. The primitive state of enzyme chemistry at the 

 turn of the century, and the lack of well-defined nucleic acids and of reliable 

 analytical methods, are responsible for this delay. ^ 



Decomposition of nucleic acids into the constituent components was 

 described toward the end of the nineteenth century, and the result was at- 

 tributed to just one enzyme, nuclease. The complexity of enzyme action in 

 such experiments with crude tissue homogenates or extracts became known 

 much later. The beginning of a systematic mapping of the enzymes as to 

 their range of action and their occurrence in various types of cells dates 

 from the work of Levene- and Jones' in 1911. Stepwise decomposition into 

 mononucleotides, nucleosides, bases, carbohydrate, and phosphoric acid 

 was found. It seemed logical to assume that the steps observed in nucleic 

 acid degradation constituted the reverse of what happened originally in 

 their biosynthesis. This concept has dominated the thinking of most investi- 

 gators, and it has remained without challenge until fairly recently. 



In general, nucleic acid investigations have followed the trend of other 

 branches of enzymology in the inadvertent emphasis on catabolism rather 

 than anabolism. The first reports of in vitro synthesis of nucleosides and 

 nucleotides appeared only a few years ago. Investigations of deamination, 

 dephosphorylation, and similar catabolic reactions still outnumber by far 

 the attempts to bring about the synthesis under controlled conditions. The 

 concept of the reversibility of all these reactions, i.e., the identity of the 

 routes of catabolism and anabolism, may be useful, if we remain ready to 

 change our concepts as future experimental results may call for revisions. 



The developments of the type to be discussed in this chapter have gained 

 momentum in recent years ; factors responsible for the ever-increasing num- 

 ber of investigations are : the growing interest of many branches of biological 

 science in nucleic acids; the progress in the neighboring field of coenzyme 

 nucleotides; the development of analytical procedures such as tracer tech- 

 niques, chromatography, and differential spectrophotometry. Further in- 

 terest has been stimulated by the observation that some vitamins function 

 in enzymatic nucleic acid assembly. 



2. Significance of Nucleosides and Nucleotides as 

 Intermediates of Polynucleotide Synthesis 



Investigators of the past have assumed that nucleic acid synthesis is the 

 reverse of enzymic disintegration. The sequence suggested was stepwise 

 combination of the bases with ribose or deoxyribose, followed by attach- 

 ment of phosphoric acid and formation of internucleotide linkages to yield 



^ W. Jones, "Nucleic Acids." Longmans, Green & Co., London, 1920. 

 2 P. A. Levene and F. Medigreceanu, J. Biol. Chem. 9, 65, 375, 389 (1911). 

 ' W. Jones, J. Biol. Chem. 9, 169 (1911). 



