Discussion on Phosphorylation 



H. M. KALCKAR 



Washington University, St. Louis, Chairman 



Dr. Kalckar: 



It seems advisable to begin this discussion on phosphorylation 

 with a brief survey of the major present-day problems in this field. 

 The mechanism of the compulsory coupling between oxidation of 

 triose and phosphorylation of adenosine nucleotides was solved 

 when Warburg and Christian isolated and crystallized the catalyst 

 of the phosphotriose oxidation and Negelein and Bromel isolated 

 the 1,3-diphosphoglyceric acid. Warburg and his collaborators also 

 demonstrated the transfer of the phosphate from the carboxyl group 

 to adenosinediphosphate. Both the oxidation process (1) and the 

 phosphate transfer are easily reversed reactions: 



O 



I II II II 



(1) c=0-t-HO— P— 0'+ pyridinium ^ — C— O— P— 0'+ reduced pyridine 



I I I 



O' O' 



o 



(2) — C — P — 0'+ adenosinediphosphate "'<=± — C + adenosine?r?phosphate"" 



1 I I 

 O O' O' 



These two reversible reactions explain completely the findings of 

 Needham, Meyerhof, and others that the utilization of the labile 

 phosphate in adenosinetriphosphate determines the extent of oxida- 

 tion of phosphotriose. 



Lipmann's observations of the formation of acetylphosphate in 

 the bacterial pyruvate oxidation furnished another important ex- 

 ample of carbonyl oxidation coupled with phosphate uptake. 



Carbonyl oxidation is not the only type of oxidation that is coupled 

 with phosphorylation. Oxidations of fumaric acid or even of succinic 

 acid are coupled with phosphorylations, but the mechanism of these 

 reactions has not been clarified. 



It has been mentioned that the extent of triose oxidation was auto- 

 matically regulated by the removal of labile phosphate in adenosine- 



190 



