Glycolysis The Pasteur Effect

Experiments with perfused rat heart have demonstrated that physiologic concentrations of citrate inhibit glycolysis by potentiating ATP inhibition of phosphofructokinase. This factor might permit additional modulation of glycolysis by the oxidation of pyruvate, fatty acids, and ketone bodies, each of which could increase citrate concentration. Of course, the actual diminution of glucose utilization relates to an inhibition of hexokinase in response to the elevated glucose-6-phosphate concentration which occurs consequent to the inhibition of PFK. 

Another important inhibitor of PFK activity is 3-phosphoglyceric acid (3-PGA). As the citrate concentration reflects the availability of fuels in the tricarboxylic acid cycle, so does the 3-PGA concentration reflect the level of metabolites at the terminal sequence of the glycolytic pathway. In this fashion, additional information is available to the cell to modulate the rate of glycolysis in accordance with its ever-changing needs. 

In addition to the postulated roles of the modulation of PFK and hexokinase activity in mediating the Pasteur effect. Packer (1975) has proposed a role for G-3-PD. In this instance, the effector molecule would be NADH, which exerts an allosteric inhibition of G-3-PD activity. Since NADH is one immediate product of the reaction, its modulating effect is not a classic example of feedback inhibition. Nonetheless, it may play a role akin to that of other servomechanisms in regulating flux through the glycolytic pathway. 

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