Effect of exercise on citrate synthase activity and expression in cardiac muscles

Citrate synthase is one of the key regulatory enzymes in the energy-generating metabolic pathway that catalyzes the condensation of oxaloacetate and acetyl coenzyme A to form citrate in the tricarboxylic acid cycle. It has been extensively used as a metabolic marker in assessing oxidative and respiratory capacity.

Although several studies have been conducted to determine the influence of exercise training in the mitochondrial enzyme adaptation in cardiac muscles, the molecular mechanism for citrate synthase adaptation to endurance training is not well understood. Adaptive elevation in the mitochondrial protein content by exercise training is suggested to be due to an increase in the rate of protein synthesis rather than a decrease in the rate of protein degradation. It raises the possibility that the modulation of mitochondrial enzyme expression in response to physical exercise is regulated by pretranslational, translational, and/or posttranslational control mechanisms. In fact, an increase in any particular mRNA concentration may signal an increased synthesis of that particular protein.

The majority of previous studies suggest that the training-induced alteration of mitochondrial enzymes is not noticeable in cardiac muscle, a few discrepant results regarding the changes were reported.

Siu et al. demonstrated a higher level of CS mRNA in cardiac ventricle muscle after exercise compared with sedentary control animals. We have shown that there is ∼20% upregulation of CS gene transcription in the ventricle muscle in response to exercise. However, interestingly, unaltered cardiac CS activity was reported in these trained animals compared with the sedentary control animals. The mechanism(s) responsible for the upregulation of ventricle CS gene transcription but without elevated CS activity is unknown. It is also possible that pre-translational mechanisms and CS turnover modulation could explain our observations (Siu, Donley et al. 2003).