506 NIACIN 



mechanism which can account for the synthesis of this fragment has been 

 described by Rowen and Kornberg.^^^ A reversible reaction which is cata- 

 lyzed by an enzyme preparation from hog liver and which requires ortho- 

 phosphate was observed. 



Nicotinamide-riboside -f orthophosphate 



^ Nicotinamide -|- ribose-1 -phosphate + H"*" 



The further reaction is tentative, but prehminary evidence indicates a 

 direct phosphorylation of nicotinamide riboside by ATP: 



Nicotinamide-riboside -|- ATP ^ Nicotinamide-riboside-phosphate -|- ADP 



5. Biosynthesis of DPN 



The biosynthesis of DPN had been observed in erythrocytes as described 

 earher and in yeast fermentation systems. ^^^ Kornberg and associ- 

 ates^^- ^^*- ^^^ have observed the following reversible reaction in a purified 

 enzyme system: 



Nicotinamide-ribose-phosphate -|- ATP <=± DPN -f inorganic pyrophosphate 



This reaction has been confirmed, with P^^ as a tracer."^ From the kinetics 

 of this reaction and the concentration of the enzyme in liver, Kornberg"^ 

 estimates that the entire DPN content of hver could be synthesized in 

 less than 5 minutes if the substrates were optimal. It can be seen that this 

 reaction not only completes DPN synthesis but provides an origin for the 

 adenine-ribose-phosphate portion of the molecule, i.e., from ATP. The 

 mechanism of adenine biosynthesis is obscure, except that it is known to be 

 synthesized by mammalian tissues. 



6. Biosynthesis of TPN 



The biosynthesis of TPN from nicotinamide plus ribose and adenosine- 

 triphosphate (ATP) in cell-free extracts has been reported.'" This report 

 has never been confirmed, and subsequent experience leaves considerable 

 doubt as to its validity. It is known that TPN can be synthesized enzymat- 

 ically from DPN*^' '^^ when DPN is incubated with ATP and a yeast 

 preparation. Mehler et al?'' also observed the formation of TPN from DPN 

 and ATP in crude liver fractions. The mechanism of this reaction has now 

 been shown to be a direct phosphorylation of DPN by ATP which is cata- 

 lyzed by an enzyme which can be purified from ale yeast. ^^ 



DPN -I- ATP -^ TPN + adenosinediphosphate (ADP) 



1^5 A. Kornberg, in Phosphorus Metabolism, Chapter VI. The Johns Hopkins Press, 



Baltimore, 1951. 

 166 A. Lennerstrand, Arkiv Kemi, Mineral. Geol. 14A, No. 16, 1 (1941). 

 1" K. I. Altman and E. A. Evans, Jr., J. Biol. Chem. 169, 463 (1947). 

 "8 H. von Euler and R. Vestin, Arkiv Kemi, Mineral. Geol. 12B, No. 44 (1938). 



