Pyruvate dehydrogenase is inhibited by which compounds during the fasting state?

Pyruvate dehydrogenase (PDH) plays a crucial role in cellular metabolism, particularly in converting pyruvate into acetyl-CoA, which then enters the citric acid cycle for energy production. During the fasting state, the regulation of metabolic pathways shifts to prioritize the conversion of energy stores over immediate energy production from glucose.

In this context, PDH is inhibited by high levels of its products. Acetyl-CoA and NADH are both indicators of an increased availability of fatty acids and a response indicating sufficient energy production. When acetyl-CoA levels are high, it suggests that the body does not need to convert more pyruvate into acetyl-CoA for energy, and thus PDH is inhibited to prevent unnecessary substrate conversion that could lead to excess ketone body production in the liver. Similarly, high NADH levels indicate an abundance of reducing equivalents, suggesting that the energy state of the cell is already high, prompting inhibition of PDH.

This regulatory mechanism is essential during the fasting state, where the body often relies on fat oxidation for energy rather than glucose metabolism, allowing for the conservation of essential substrates and prioritization of energy production from reserves.