SEVERO OCHOA 



action of this system (5,9,1 1,12) involves the reversal of the decarboxy- 

 lation of oxalacetic acid to pyruvic acid (reaction Ila). Reaction Ila 



OXALACETIC CARBOXYLASE 

 CH, COOH 



i I 



CO + CO2 , GH2 



I I (Ila) 



COOH CO 



I 

 COOH 



Pyruvic acid Oxalacetic acid 



is catalyzed by oxalacetic carboxylase, an enzyme which is found in 

 bacteria and liver and requires magnesium or manganese ions for 

 activity. As in the case of oxalosuccinic carboxylase, the equilibrium 

 of reaction Ila is very far to the left. Reversibility has been demon- 

 strated by allowing the enzyme to act on oxalacetic acid in the presence 

 of isotopic carbon dioxide. By stopping the enzyme action when 

 about half of the oxalacetic acid was decarboxylated, the presence of 

 isotopic carbon in the /S-carboxyl group was demonstrated. 



The equilibrium constant of reaction Ila has been calculated 

 from its free energy change, in turn calculated from the free energies 

 of formation (at 38 ° C.) of the substances involved (5) : 



oxalacetate + H2O > pyruvate" -\- HCOa" 



-184,210 cal. -56,200 cal. -106,460 cal. -139,200 cal. 



AF thus calculated is —5250 cal. for the decarboxylation, and A"a = 

 (oxalacetate — )/ (pyruvate") (HCO3-) = 0.2 X 10"^ a value of the 

 same order of magnitude as that of reaction la. 



Step 2 occurs when both malic dehydrogenase (see Table I) 

 and reduced diphosphopyridine nucleotide are present, since the 

 oxalacetic acid formed by reaction Ila is then reduced to /-malic 

 acid (reaction lib). 



MALIC DEHYDROGENASE 

 COOH COOH 



CH2 CH2 



I + DPNH2 , I + DPN (Hb) 



CO CHOH 



COOH COOH 



Oxalacetic acid /-Malic acid 



176 



