Anaplerosis and gluconeogenesis — The mitochondrial conversion of pyruvate to oxaloacetate (OAA) by pyruvate carboxylase has which of the following features?
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AIt requires the cofactor biotin (vitamin B7)
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BIt involves fixation of carbon dioxide (as bicarbonate) into the oxaloacetate product
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CIt occurs in the mitochondrial matrix in most tissues (e.g., liver)
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DAll of the above
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ENone of the above
Answer
Correct Answer: All of the above
Explanation
Introduction:Pyruvate carboxylase catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, providing an anaplerotic entry to the TCA cycle and the first committed step of gluconeogenesis. This question reviews the essential requirements and localization of this reaction.
Given Data / Assumptions:
- Pyruvate carboxylase is a biotin-dependent enzyme.
- CO2 (as bicarbonate, HCO3−) is incorporated into pyruvate to form oxaloacetate.
- The reaction occurs in the mitochondrial matrix and is activated by acetyl-CoA.
Concept / Approach:Confirm the cofactor (biotin), the chemistry (carboxylation/fixation of CO2), and subcellular localization (mitochondria). If all statements are true, the comprehensive answer is “All of the above.”
Step-by-Step Solution:
Recognize reaction: pyruvate + CO2 + ATP → oxaloacetate + ADP + Pi.Biotin serves as a CO2 carrier on a lysine prosthetic arm.The enzyme resides in the mitochondrial matrix; OAA may be shuttled to cytosol as malate/aspartate for gluconeogenesis.Verification / Alternative check:Biotin deficiency impairs anaplerosis/gluconeogenesis; mitochondrial isolation studies locate pyruvate carboxylase activity in the matrix.
Why Other Options Are Wrong:
a–c) Each is correct individually, so the best overall choice is d.e) Contradicted by established biochemistry.Common Pitfalls:Forgetting acetyl-CoA is an allosteric activator; confusing cytosolic PEPCK with mitochondrial pyruvate carboxylase localization.
Final Answer:All of the above.