Give an Overview of Urea Cycle
The urea cycle, also known as the ornithine cycle, is a series of biochemical reactions that occur in the liver to convert toxic ammonia into urea, which is then excreted in the urine. It is the primary pathway for nitrogen excretion in ureotelic organisms, including humans.
Importance of Urea Cycle
- Removes excess nitrogen resulting from amino acid breakdown
- Prevents accumulation of toxic ammonia in the body
- Regulates nitrogen balance
Steps of Urea Cycle
- Formation of Carbamoyl Phosphate: Ammonia (NH₃) and carbon dioxide (CO₂) react in the mitochondria, catalyzed by carbamoyl phosphate synthetase I (CPS I), requiring ATP.
- Formation of Citrulline: Carbamoyl phosphate reacts with ornithine to form citrulline, catalyzed by ornithine transcarbamylase. Citrulline is transported to the cytosol.
- Formation of Argininosuccinate: Citrulline combines with aspartate, forming argininosuccinate in a reaction catalyzed by argininosuccinate synthetase (requires ATP).
- Formation of Arginine: Argininosuccinate is cleaved by argininosuccinate lyase into arginine and fumarate.
- Formation of Urea: Arginine is hydrolyzed by arginase to produce urea and regenerate ornithine, which re-enters the mitochondria.
Overall Reaction
2 NH₃ + CO₂ + 3 ATP + H₂O → Urea + 2 ADP + 4 Pi + AMP + Fumarate
Regulation
- Stimulated by high protein intake and during starvation
- N-Acetylglutamate acts as an allosteric activator of CPS I
Disorders of the urea cycle can lead to hyperammonemia, a dangerous condition that requires immediate medical intervention.