CARBON DIOXIDE 



essential or even important for heterotrophic organisms and animal 

 cells. One could conceive, however, that fixation might be used for 

 the synthesis of special cell constituents such as growth factors or the 

 like. It is well known that most heterotrophic bacteria require the 

 presence of carbon dioxide in the medium for optimal growth. 



The cellular mechanisms of carbon dioxide fixation have been 

 obscure for a long time. It is only recently that light has been shed 

 on the mechanism by which fixation occurs in heterotrophic bacteria 

 and animal cells. As it now appears, the fundamental process in all 

 types of carbon dioxide fixation is a reversal of the decarboxylation of 

 some keto acids — a process catalyzed by enzymes. These reactions 

 are reversible, but their equilibrium lies very far to the side of decar- 

 boxylation, i. e., liberation of carbon dioxide. Thus, the problem faced 

 by the cell is to shift the equilibrium as far as possible in the opposite 

 or uphill direction, and this requires expenditure of energy. 



It has been established (15) that the free energy change of a re- 

 versible chemical reaction is related to the equilibrium position in a 

 manner expressed by the equation: 



^F = -RT In K 

 where AF represents the change in free energy (expressed in gram 

 calories) and K is the equilibrium constant. If the equilibrium con- 

 stant is expressed as: 



(decarboxylation product) (CO2) 

 (carboxylated product) 

 The equilibrium constant of some of the reversible decarboxylations is 

 of the order of 10^, so that they proceed with a decrease in free energy 

 of about —4000 to —5000 calories. Here are included the enzymic 

 decarboxylation of oxalacetic acid to pyruvic acid and carbon dioxide, 

 and that of oxalosuccinic acid to a-ketoglutaric acid and carbon di- 

 oxide. In both cases the reaction involves a carboxyl in position 

 /3 relative to the carbonyl group; this reaction type will be referred to 

 here as j3-carboxylation. 



There is another group of enzymic decarboxylations involving 

 simultaneous decarboxylation and dehydrogenation of a-keto acids 

 that proceed with a much larger decrease in free energy than do /3- 

 decarboxylations. Thus, the free energy change of reaction (1): 

 pyruvate- + 2 H2O <^ acetate" + HCO3 " + 3 H+ + 2 e (1) 



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