76 S, S. COHEN 



NRP + ARPPP NRPPRA + PP 



nirotinaniide ribose phosphate + adenosine triphosphate ^ DPN -\- pyrophosphate 



Thus, unless anotlier mechanism is found for the biosynthesis of DPN, it 

 can be assumed that the coenzyme is transferred to the cytoplasm from its 

 primary site of synthesis. Furthermore, since the sucrose method used 

 usually results in a marked loss of protein, it would appear that this enzyme 

 is confined to some site from which it does not leach. It has been reported that 

 nucleoh isolated from the starfish contam a very high concentration of this 

 enzyme (Baltus, 1954). However, it has been observed that in amoebae, 

 enucleation does not produce a decrease in DPN content after 168 hours 

 (Cohen, A., 1956). It is possible that cytoplasmic DPN may be highly stable 

 m tins organism since no turnover data are available for this system. Jacob- 

 son and Kaplan (1957b) have demonstrated a DPNH pyrophosphatase in the 

 soluble fraction of mammalian liver, and DPN pyrophosphatase and DPNase 

 in the microsomal fraction. 



DPN is an essential component of the Embden-Meyerhof glycolytic 

 system and it has been found that wheat germ nuclei are capable of meta- 

 bolizing hexose diphosjihate to pyruvate anaerobically with an activity 

 comparable to that of cytoplasm (Stern and Mirsky, 1952, 1953). Indeed, 

 enolase and pyruvate kinase are highly concentrated in these nuclei, and in 

 calf fiver nuclei, as well. In addition to these enzymes of carbohydrate 

 metabolism, the first step in the phosphogluconate pathway, glucose-6- 

 phosphate dehydrogenase, is also highly active in plant and animal nuclei. 

 The first steps of this system require triphosphopyridine nucleotide (TPN) 

 in most cells and the presence of this coenzyme in rat liver nuclei has also 

 been recorded recently (Jacobson and Kaplan, 1957a). The distribution of the 

 oxidized and reduced forms of these coenzymes in rat liver nuclei and other 

 cell components have also been recorded by these authors. These coenzpnes 

 do not appear to be present in considerable amounts in nuclei despite their 

 apparent origin in this organelle. However, it is not certain to what extent 

 these substances were destroyed in isolation, nor is it known whether these 

 substances may not have been leached from the nuclei during isolation, 

 leading to their apparently high concentration m the cell sap. 



Numerous reports have mdicated that neoplastic tissues have a relatively 

 low content of DPN. The synthesis of TPN from DPN also appears to be 

 curtailed in tumor cells (Glock and McLean, 1957). It may be asked, there- 

 fore, if tumor cells are not deficient in the capacity to synthesize these 

 coenzymes, since the diphosphopyridine nucleotidase activity of a variety 

 of tumors is within the range of normal tissue activities. Alternatively, the 

 nucleotide substrates for DPN and TPN synthesis may have been shunted to 

 the other syntheses occurring in such cells. This question is currently of 

 considerable interest to virologists, in view of the observed dedifferentiation 



