Question

During vigorous exercise, how is skeletal muscle pyruvate dehydrogenase regulated to increase its level of activity?

In your response include metabolites that affect PDH kinase and therefore the activity of PDH.

Answer 1

During exercise, the activation of pyruvate dehydrogenase in human skeletal muscle is regulated by three metabolites

a.Increases in Ca2+,

b.Increase in free ADP

c. Concentration of pyruvate

During resting phase the high ATP/ADP, NADH/NAD, and acetyl-CoA/CoA ratios and the low pyruvate levels leads to a high PDH kinase activity. On the other hand, lower concentration of Ca2+ leads to a low PDH phosphatase activity. In this state PDH is in the inactive form. During exercise, increases in Ca2+, pyruvate and free ADP contribute to the activation of PDH . Due to the increase in the free ADP concentration the ATP turnover is increased which in turn ,plays an important role in activation of enzymes involved in oxidative phosphorylation, glycogenolysis, glycolysis, PDH, and the TCA cycle. This eventually increases the glycolytic flux and also increases the production of pyruvate, which again activates PDH