154 S. S. COHEN 



compounds. Although, we know of instances, e.g., acety]-SCoA, in which 

 important facets of metabolism appear to by]3ass phosphate metabohsm, 

 such knowTi reactions are still proportionately few and, in any case, soon 

 merge with aspects of phosphate metabohsm in the metabohsm of the living 

 ceU. The mechanisms of the continuous attachment and transfer of phosphate 

 must evidently be of great concern m our understandmg of biological 

 systems. 



1. Hydrolases and Transferases 



Mention has been made above of mechanisms by which inorganic phosphate 

 and pyrophosphate may be used to form low molecular organic phosphates. 

 Numerous examples will be given below of these reactions m coenzyme and 

 polymer formation. In addition, numerous enzymatically catalyzed reactions 

 of phosphate exchange have been recognized among the low molecular 

 organic phosjDhates. For example, ribose 1, 5 diphosphate will transfer the 

 1 phosphate to the 5 position of ribose- 1 -phosphate, as follows: 



ribose* 1, 5 diphosphate + ribose-1 -phosphate ^ ribose*-5-phosphate + ribose- 



1, 5-cliphosphate 



An enzyme can thereby facUitate the transfer of phosphate to the primary 

 hydroxyl of a sugar moiety. It can be imagined that if the transfer of the 

 group had been effected to water, the enzyme would be considered to be a 

 phosphatase, which is commonly thought of as a hydrolytic enzyme. Thus, 

 the type of reaction produced would be deternuned m part by the s^^ecificity 

 of the requirement of the enzyme for certain acceptors. Conversely, then, it 

 can be supposed that some hydrolytic enzymes might effect group transfers 

 to acceptors other than water. Such reactions have mdeed been fomid and 

 many so-called phosphatases are now known to catalyze phosphoryl transfer, 

 as summarized by Axelrod (1956b). For example, alkahne phosphatase can 

 transfer phosphate from a sugar phosphate, such as glucose-6-phosphate, to 

 alcohols and phenols. In extending this phenomenon, it has been found that 

 phosphates can be transferred from phosphate esters of various alcohols to 

 nucleosides and nucleotides by phosphotransferases of a wide variety of 

 tissues and organisms: 



phenyl phosphate (cPP) + uridine > phenol + uridine-5'-phosphate 



^P + uridine-2'-phosphate > phenol + uridine-2' 5'-diphosphate 



Although the role of such systems in metabohsm is not clear, it is significant 

 that 5' nucleotides can serve as phosphate donors and, m transfer of the 

 phosphate from these nucleotides to nucleosides with plant and bacterial 

 enzymes, the products are predominantly 5' nucleotides (Tunis and Chargaff, 

 1956). Pancreatic ribonuclease, a diesterase, also effects nucleotide transfer 

 as a result of phosphate transfer, as weU as hydrolytic cleavage. The existence 



