Biochemistry · Amino Acid Metabolism and Urea Cycle (Disorders, Phenylketonuria)

Argininosuccinate lyase releases fumarate into the cytosol. How does this fumarate re-enter central metabolism?

  • A It is exported directly into the mitochondrial matrix through the malate-aspartate shuttle
  • B It is carboxylated by pyruvate carboxylase to form oxaloacetate
  • C It is reduced to succinate by succinate dehydrogenase in the endoplasmic reticulum
  • D Cytosolic fumarase converts it to malate, then cytosolic malate dehydrogenase forms oxaloacetate, which can be transaminated to aspartate
Correct answer: D. Cytosolic fumarase converts it to malate, then cytosolic malate dehydrogenase forms oxaloacetate, which can be transaminated to aspartate

Explanation

The urea and Krebs cycles are linked by fumarate. Cytosolic fumarase hydrates it to malate, and cytosolic malate dehydrogenase oxidizes malate to oxaloacetate, which transamination converts back to aspartate, closing the nitrogen-transfer loop. Option A is wrong because fumarate crosses membranes poorly and is metabolized where it is released; option B confuses anaplerosis at pyruvate with fumarate handling.

Reference: Lippincott's Illustrated Reviews: Biochemistry, 8th ed.

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