Biochemistry Module 6 Practice Exam 2026 - Free Biochemistry Practice Questions and Study Guide

PDH activity is controlled by the cell’s energy state. When energy is high, signals such as NADH and acetyl-CoA accumulate, and ATP is abundant. These signals promote PDH kinase activation, which phosphorylates and inactivates the pyruvate dehydrogenase complex. This keeps pyruvate from being converted to acetyl-CoA, matching metabolism to the low need for further carbon entry into the TCA cycle. Conversely, when energy demand rises, PDH phosphatase is activated (by signals like Ca2+ and insulin), removing the inhibitory phosphate and activating PDH.

So inhibition of the complex is not driven only by ATP; high NADH and high acetyl-CoA also contribute, through increased phosphorylation by PDH kinase. In addition, ADP/AMP signals would tend to promote activation rather than inhibition, and inhibition can be relieved when the cell needs more carbon entry into the cycle.