Urea cycle — The two nitrogen atoms in urea are derived from which sources?

Introduction / Context:
The urea cycle detoxifies ammonia by converting it to urea for excretion. Understanding the origin of urea’s two nitrogen atoms helps clarify the flow of nitrogen from amino acid catabolism to excretion.

Given Data / Assumptions:

• Urea has two nitrogens and one carbon (CO(NH2)2).
• Ammonia arises from oxidative deamination and other reactions.
• Aspartate donates an amino group via transamination pathways.

Concept / Approach:
One nitrogen enters as free ammonia (NH3/NH4+) when carbamoyl phosphate is formed from NH3 and CO2. The second nitrogen is donated by aspartate during the argininosuccinate step, ultimately appearing in urea after cleavage of arginine by arginase.

Step-by-Step Solution:

Verification / Alternative check:
Isotopic labeling shows one 15N from ammonia and one 15N from aspartate incorporated into urea in hepatocytes.

Why Other Options Are Wrong:

• Nitrate and nitrite are not used as nitrogen donors in human urea formation.
• “Ammonia” alone accounts for only one nitrogen.

Common Pitfalls:
Confusing aspartate’s role as a nitrogen donor with its carbon skeleton fate; the carbon backbone leaves as fumarate.

Final Answer:
Ammonia and aspartic acid