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

A patient is infused with 15N-labelled aspartate before an assay of newly formed urea. Where will the labelled nitrogen appear?

  • A In neither nitrogen atom of urea
  • B In both nitrogen atoms of urea
  • C In one nitrogen atom of urea, donated at the argininosuccinate synthetase step
  • D Only in the carbon skeleton, never in the urea nitrogen
Correct answer: C. In one nitrogen atom of urea, donated at the argininosuccinate synthetase step

Explanation

Urea contains two nitrogens: the first arrives as free ammonia incorporated by CPS-I, while the second is contributed by the amino group of aspartate during the argininosuccinate synthetase reaction. Aspartate therefore donates exactly one labelled nitrogen per urea molecule. This dual-source design explains why defects in aspartate supply, such as citrin deficiency, also produce hyperammonemia despite normal CPS-I activity.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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