Pyruvate Dehydrogenase Notes

Pyruvate Dehydrogenase (PDH)

Role of Pyruvate Dehydrogenase

• Pyruvate, produced from aerobic glycolysis, enters the mitochondria.
• In the mitochondria, pyruvate can be converted into acetyl CoA.
  • If ATP is needed, acetyl CoA enters the citric acid cycle.
  • If sufficient ATP is present, acetyl CoA is used for fatty acid synthesis.
• The pyruvate dehydrogenase complex (PDH) reaction is irreversible.
  • Acetyl CoA cannot be converted back to pyruvate or glucose via PDH.

Regulation of Pyruvate Dehydrogenase

• Liver:
  • Activated by insulin.
  • High insulin levels indicate a well-fed state.
  • The liver should burn glucose for energy and shift the fatty acid equilibrium toward production and storage.
• Nervous System:
  • PDH is not responsive to hormones like insulin.

Fatty Acid Synthesis

• Starts from citrate produced in the citric acid cycle.
• Refer to chapter 11 of MCAT biochemistry review for details.

Pyruvate Dehydrogenase Complex

• PDH is a complex of enzymes that carry out multiple reactions.
• Details of these reactions are in chapter 10 of MCAT biochemistry review.
• Represents one of three possible fates of pyruvate:
  • Conversion to acetyl CoA by PDH.
  • Conversion to lactate by lactate dehydrogenase.
  • Conversion to oxaloacetate by pyruvate carboxylase.

Cofactors and Coenzymes Required

• Thiamine pyrophosphate
• Lipoic acid
• CoA
• FAD
• NAD+
• Insufficient amounts can cause metabolic derangements.

Inhibition of Pyruvate Dehydrogenase

• Inhibited by its product, acetyl CoA.
• Important control mechanism along with pyruvate carboxylase.
• Buildup of acetyl CoA (e.g., during beta oxidation):
  • Shifts metabolism away from converting pyruvate to acetyl CoA for the citric acid cycle.
  • Favors conversion of pyruvate to oxaloacetate for gluconeogenesis.