12 A SYMPOSIUM ON RESPIRATORY ENZYMES 



mediary, and consequently we have three consecutive steps (25). 

 The overall reaction goes from left to right or in the opposite direc- 

 tion, depending upon the concentration of the reactants (Figure 4). 

 If, for instance, adenosinetriphosphate is continuously resynthesized 

 by an independent reaction, so that its concentration remains high 

 and the concentration of the inorganic phosphate low, the reaction 

 is pushed in the direction of the reduction of phosphoglyceric acid. 

 This reaction is favored still further if the phosphoglyceraldehyde 

 is removed by isomerisation to dihydroxyacetonephosphate and by 

 condensation to hexosediphosphate and so on. In this way the syn- 

 thesis can actually take place. 



There remains one reaction which in the light of experiments 

 with radioactive phosphorus, seems to be irreversible— the dephos- 

 phorylation of phosphopyruvic acid. Adenosinetriphosphate con- 



I. Stoichiome trie-coupled reaction (Meyerhof, Ohlmeyer, Kiessling, 1937-38) 



( Co=cozymase ) 



(i-3-Phosphoglyceraldehyde+Co-|-Adenosinediphosphate+H3P04?=^ 

 d-3-Phosphoglyceric acid+CoH2+ Adenosinetriphosphate 



II. Warburg and Christian's explanation of the coupled reaction ( 1939 ) 



A. d-3-Phosphoglyceraldehyde+H3P04?^l,3-Diphosphoglyceraldehyde (?) 



B. l,3-Diphosphoglyceraldehyde+Co<^l,3-Diphosphoglyceric acid-j-CoHj 



C. 1,3-Diphosphoglyceric acid+Adenosinediphosphate<^ 

 3-Phosphoglyceric acid+ Adenosinetriphosphate 



Figure 4. — Coupling of phosphorylation and oxidoreduction 



taining radioactive phosphorus in its labile groups did not exchange 

 this radioactive phosphorus with phosphopyruvic acid. If the reac- 

 tion between phosphopyruvic and adenylic acid were reversible, an 

 exchange should have taken place. But we must concede that the 

 experimental basis for this negative result is not too large and there- 

 fore accept it with some reservation until it is more firmly estab- 

 lished. If for the moment we accept the result, it has important im- 

 plications. There is indeed reason to believe that the oxidation of 

 carbohydrate by way of the four-carbon acids intervenes to bring 

 pyruvic acid back to phosphopyruvic. Some years ago Kalckar ob- 

 served, during oxidation of fumarate by kidney extract, the formation 

 of an acid which seemed phosphopyruvic (26). The more recent 

 findings of several investigators (27, 28, 29, 30) on the assimilation 

 of isotopic carbon dioxide, which appears in oxalacetic and keto- 

 glutaric acid and in glycogen during synthesis from lactic acid, fit 

 very well into such a scheme. Now that the condensation of carbon 



