Which of the following downregulates pyruvate dehydrogenase by covalently modifying the enzyme complex? ATP Acetyl CoA AMP ADP Calcium ions

The regulation of pyruvate dehydrogenase (PDH) is an important aspect of cellular metabolism, specifically in the conversion of pyruvate to acetyl CoA. Pyruvate dehydrogenase is subject to covalent modification, notably phosphorylation, which inactivates the enzyme.

1. Covalent Modification Role: The enzyme is modified via a kinase that adds a phosphate group (phosphorylation) to the pyruvate dehydrogenase complex, thereby inhibiting its activity. Conversely, a phosphatase can remove that phosphate group, activating the enzyme.

2. Key Regulators: Among the listed options, ATP, Acetyl CoA, AMP, ADP, and calcium ions can influence PDH activity, but in the context of downregulation through covalent modification:

   • ATP and Acetyl CoA are known to promote phosphorylation of PDH.
   • Calcium ions and AMP, on the other hand, generally signal the need for increased energy production, promoting the activation of PDH.

3. Final Determination: Therefore, the correct answer to which of these downregulates pyruvate dehydrogenase by covalently modifying the enzyme is ATP and Acetyl CoA, as they lead to phosphorylation of the enzyme, resulting in its inactivation.

Final Answer

ATP and Acetyl CoA downregulate pyruvate dehydrogenase by covalently modifying the enzyme complex.