588 G. SCHMIDT 



significant parallelism with their toxicity. The activity of these enzymes is 

 strongly inhibited by some factors known to depress the toxicity, such as 

 antivenom serum, cysteine, and formaldehyde. The activity determinations 

 of Taborda's group were carried out on crude extracts; since a manometric 

 method was used, the values obtained represent figures of the phosphodi- 

 esterase activities. 



-pH Optimum. The optimum for the hydrolysis of PNA and of deoxy- 

 oligonucleotides is at pH 9.2. ^^^'^^^ GuUand and Jackson reported optimum 

 hydrolysis of diphenyl phosphate at pH 8.6.^^* 



Activators and inhibitors. Snake venom phosphodiesterase is considerably 

 activated by 0.003 M magnesium ions, and to a lesser extent by manganese 

 ions. Its activity seems to be inhibited by the characteristic inhibitors of 

 alkaline phosphomonoesterases such as cyanide and cysteine, but the evalu- 

 ation of the available data is difficult because of the high concentrations 

 at which the inhibitors were studied. Adrenocorticotropic hormone and 

 cortisone, both of which are known to alleviate the clinical toxicity of the 

 venoms, has no effect on their phosphodiesterase activity, 



h. ^^Phosphodiesterase" of Intestinal Mucosa 



The studies of the enzymic cleavage of nucleic acids into lower poly- 

 nucleotides and mononucleotides by duodenal juice or by extracts of in- 

 testinal mucosa were of great historical importance in the development of 

 the chemistry of the nucleic acids. The use of this enzyme for the partial 

 hydrolysis of nucleic acids in the laboratory of P. A. Levene"^ and in that of 

 S. J. Thannhauser^'^ was essential for the successful isolation of the nu- 

 cleosides and nucleotides of deoxyribonucleic acids and for the isolation of 

 D-deoxyribose. After the advent of ion-exchange chromatography, Cohn 

 and Carter^^" succeeded for the first time in isolating the four 5'-ribonucleo- 

 tides as products of the enzymic hydrolysis of PNA by intestinal phospho- 

 diesterase. 



Specificity. Unlike snake venom phosphodiesterase, intestinal phospho- 

 diesterase has not been obtained free from phosphomonoesterase activity 

 by fractionation methods."' "' The phosphodiesterase activity of highly 

 purified preparations of intestinal phosphatase is specific toward the bonds 

 between the nucleotide groups of PNA and those of DNA polynucleotides 

 of relatively low molecular weights. Cyclic 2',3'-mononucleotides are not 

 hydrolyzed by intestinal phosphodiesterase.^^ Diphenyl phosphate, glyc- 



''* P. A. Levene and L. W. Bass, "Nucleic Acids." Chemical Catalog Co., New York, 



1931. 

 139 W. Klein and S. J. Thannhauser, Z. physiol. Chem. 231, 96 (1935). 

 1^0 W. E. Cohn and C. E. Carter, Nahire 167, 483 (1951). 

 1" G. Schmidt and S. J. Thannhauser, J. Biol. Chem. 149, 369 (1943). 



