558 G. SCHMIDT 



Only a few of the known enzymes of nucleic acid metabolism have been 

 thoroughly investigated, and, as yet, only two have been obtained in 

 crystalline form. The properties of these nucleases will be discussed in 

 some detail in the following sections. Some of these enzymes have become 

 important tools for the study of the structure of nucleic acids. The wealth 

 of information accumulated during the intense recent study of ribonuclease 

 I and deoxyribonuclease I is in striking contrast to the scarcity of descrip- 

 tive data available for the majority of the enzymes of nucleic acid metab- 

 olism. A review of the present knowledge of this field is, therefore, of 

 necessity very unbalanced. It should be pointed out that the relative space 

 devoted to some individual enzymes reflects the intensity of work devoted 

 to their study, rather than the degree of their importance in nucleic acid 

 metabolism. 



II. Enzymes Catalyzing the Cleavage of Bonds Between Nucleotides 



1. RiBONUCLEASES 



a. Pancreas Ribonuclease (Ribonuclease I) 



History. In 1920, Walter Jones observed that boiled extracts of pancreas 

 were capable of transforming yeast ribonucleic acid to acid-soluble products 

 without the liberation of inorganic phosphate or of purine and pyrimidine 

 bases. ^ This observation was a decisive advance in our knowledge of nucleic 

 acid metabolism because it demonstrated for the first time the existence of 

 a specific enzyme the activity of which is limited to the cleavage of inter- 

 nucleotide bonds without the formation of ammonia, inorganic phosphate, 

 or free purines or pyrimidines. The separation of this specific activity from 

 those of the rather ubiquitous deaminases, phosphatases, and nucleosidases 

 was facilitated by the exceptional heat stability of Jones' enzyme, since at 

 the time of its discovery the technique of enzyme fractionation was very 

 primitive. The enzymic degradation of nucleic acids in pancreas had been 

 observed much earlier by Jones himself® as well as by others; but, in these 

 experiments, the hydrolysis always proceeded beyond the stage of nucleo- 

 tides. It is, therefore, justified to consider the date of the discovery of 

 ribonuclease as coincident with that of the detection of its heat stability. 

 Interestingly enough, in his first paper, Jones himself expressed doubt as 

 to whether the activity of his boiled pancreas extracts could be attributed 

 to the presence of an enzyme. This doubt was shared by his contemporaries 

 and was during a considerable period a discouraging influence on the 

 further investigation of Jones' observation. Eighteen years had elapsed 

 after the publication of Jones' paper, when interest in the heat-stable 



6 W. Jones and M. E. Perkins, Am. J. Physiol. 55, 557 (1923). 

 6 W. Jones, Z. physiol. Chem. 41, 101 (1904). 



