Bioenergetics — Under aerobic conditions in mammalian metabolism, pyruvate is converted by the pyruvate dehydrogenase (PDH) complex into which product before entering the citric acid (TCA) cycle?

Difficulty: Easy

Correct Answer: Acetyl-CoA

Explanation:


Introduction:
Aerobic carbohydrate metabolism channels the end product of glycolysis, pyruvate, into the mitochondrion for complete oxidation. This question tests your understanding of the pyruvate dehydrogenase (PDH) complex, the irreversible “gatekeeper” that converts pyruvate into a substrate suitable for the citric acid cycle.


Given Data / Assumptions:

  • Aerobic conditions are present (sufficient oxygen and active mitochondria).
  • Pyruvate is formed in the cytosol by glycolysis.
  • The PDH complex resides in the mitochondrial matrix and uses multiple cofactors.


Concept / Approach:
The PDH complex performs oxidative decarboxylation of pyruvate. It removes one carbon as CO2 and attaches the remaining two-carbon acetyl group to coenzyme A, forming acetyl-CoA. Electrons are transferred to NAD+ to yield NADH. This reaction is essentially irreversible in vivo and commits carbon to the TCA cycle and, potentially, fatty acid synthesis when energy is ample.


Step-by-Step Solution:

Transport: pyruvate enters mitochondria via the mitochondrial pyruvate carrier.Decarboxylation: E1 (pyruvate dehydrogenase with TPP) removes CO2.Transfer: E2 (dihydrolipoyl transacetylase with lipoamide/CoA) forms acetyl-CoA.Reoxidation: E3 (dihydrolipoyl dehydrogenase with FAD/NAD+) regenerates cofactors and produces NADH.


Verification / Alternative check:
PDH deficiency causes pyruvate and lactate accumulation and reduced acetyl-CoA formation, clinically validating that PDH’s product is acetyl-CoA used by the TCA cycle for ATP generation via oxidative phosphorylation.


Why Other Options Are Wrong:

  • Phosphoenolpyruvate: upstream glycolytic intermediate; not the PDH product.
  • Lactate: formed under anaerobic or high-intensity conditions via lactate dehydrogenase, not by PDH.
  • Glyceraldehyde-3-phosphate: an earlier glycolytic triose, unrelated to PDH output.
  • Oxaloacetate: a TCA intermediate synthesized by pyruvate carboxylase (biotin dependent), not PDH.


Common Pitfalls:
Confusing PDH with pyruvate carboxylase or lactate dehydrogenase. Remember: PDH requires oxygen availability and generates acetyl-CoA plus NADH and CO2.


Final Answer:
Acetyl-CoA.

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