PRIMING REACTIONS 205 



of acetyl-CoA is governed by the condensation enzyme discovered by 

 Ochoa. In the presence of this enzyme, acetyl-CoA reacts with a molecule 

 of oxaloacetate to form citric acid with the liberation of a molecule of CoA. 

 (If the concentration of oxaloacetic acid is low, as is the case in starvation, 

 diabetes, etc., two molecules of acetyl-CoA may combine to give aceto- 

 acetyl-CoA which, losing CoA, will give acetoacetate and eventually acetone 

 or other ketonic bodies). In this operation an energy-rich bond of 



CH2COOH 

 CH3— CO— S— CoA +1 + H2O 



COCOOH 



oxaloacetic acid 

 = CH2COOH 



HOCCOOH + HS— CoA 



CH2COOH 



citric acid 



ATP is consumed. However this loss is compensated by the recovery of 

 an energy-rich thioester bond in acetyl-CoA. The condensation reaction 

 has a large —AF and is practically irreversible. Reactions 3 and 4 are 

 catalysed by aconitase. A molecule of water is removed in reaction 3 with 

 the formation of a double bond, and during reaction 4 the chain is again 

 saturated with the OH at another position. Reactions 3 and 4 are reversible. 

 Reaction 5 is a reversible oxidation utilizing TPN as the coenzyme for 

 the dehydrogenase (isocitric dehydrogenase). Reaction 6 is a non-oxidative 

 decarboxylation producing a-ketoglutaric acid. The equilibrium lies far 

 to the right and is practically irreversible. It is however reversible under 

 certain conditions. Reaction 7 is an oxidative decarboxylation having 

 several characteristics in common with the decarboxylation of pyruvic 

 acid. It can be depicted as commencing with a decarboxylation accom- 

 panied by a dehydrogenation, yielding a succinyl derivative of LTPP 

 containing an energy-rich thioester linkage. This latter, in a second 

 reaction, exchanges its thioester bond with CoA to give succinyl-CoA 

 and disulphydryl-LTPP. In a third reaction, the latter gives up two 

 H atoms to DPN+ giving the disulphide form, DPNH and H+. The 

 DPNH on entering the respiratory chain gives three ATP energy-rich 

 bonds. 



