Regulation of the tricarboxylic acid cycle pool size in heart muscle.

The anaplerotic mechanisms are mainly responsible for the intricate control of the size of the total tricarboxylic acid cycle pool, since cataplerotic fluxes leading out of the cycle can even increase during net synthesis of the cycle intermediates. Pyruvate carboxylation is probably the most important anaplerotic mechanism regulating the pool size of the citric acid cycle. However, not much is known of the regulation of pyruvate carboxylation or other ana- or cataplerotic mechanisms, and further research in this area is needed. The evidence accumulated so far indicates that regulation of the tricarboxylic acid cycle pool size serves to optimize energy transduction in heart muscle. This is seen at the level of the tricarboxylic acid cycle, where the tricarboxylic acid cycle intermediates can be taken to act in a catalytic manner to adjust the activities of the individual enzymes of the cycle at an appropriate level for a certain metabolic situation. On the other hand, increase in the mitochondrial citrate content serves as the mediator between the mitochondrial and cytosolic spaces and leads to diminished glucose utilization in glycolysis due to feed-back inhibition. However, net anaplerosis does not constitute a major energy-releasing system in the ischemic myocardium.