Source of carbon in urea synthesis — In the hepatic urea cycle, which compound supplies the carbon atom of urea?

Introduction / Context:
Urea contains one carbon atom and two nitrogens. While the nitrogens derive from ammonia and aspartate, the carbon originates from CO2 (as bicarbonate). Recognizing this source clarifies how carbon and nitrogen metabolism intersect in hepatic detoxification.

Given Data / Assumptions:

• Carbamoyl phosphate synthetase I (CPS I) uses CO2 and NH3.
• The carbon in urea is the carbonyl carbon.
• Process requires ATP and occurs partly in mitochondria and partly in cytosol.

Concept / Approach:
CO2 (bicarbonate) condenses with ammonia to form carbamoyl phosphate, introducing the carbon that persists through citrulline and arginine intermediates to appear in urea. Neither arginine nor aspartate donates the carbonyl carbon of the final urea molecule.

Step-by-Step Solution:

Verification / Alternative check:
Isotopic 13C bicarbonate labeling appears in the urea carbonyl during hepatic perfusion studies, confirming the source.

Why Other Options Are Wrong:

• Arginine is a cycle intermediate cleaved to release urea; it does not supply the carbon atom de novo.
• Aspartate provides a nitrogen, not the carbonyl carbon.
• Glucose is not directly used as the carbon donor in urea formation.

Common Pitfalls:
Assuming the nitrogen donor aspartate also donates carbon; in fact, its carbon skeleton exits as fumarate.

Final Answer:
Carbon dioxide