Which enzyme catalyzes the first committed step of the urea cycle by combining ammonia with carbamoyl phosphate?

Explanation

## Urea Cycle: First Committed Step **Key Point:** Carbamoyl phosphate synthetase I (CPS I) catalyzes the first committed step of the urea cycle by condensing ammonia (NH₃) with carbamoyl phosphate to form carbamoyl ammonia. ### Reaction Details - **Substrate:** Carbamoyl phosphate + NH₃ - **Product:** Carbamoyl ammonia (carbamate) - **Location:** Mitochondrial matrix - **Cofactor:** Requires N-acetylglutamate (NAG) as an allosteric activator - **Energy cost:** 2 ATP equivalents (1 ATP + 1 GTP) ### CPS I vs CPS II | Feature | CPS I (Urea Cycle) | CPS II (Pyrimidine Synthesis) | |---------|-------------------|------------------------------| | Location | Mitochondria | Cytoplasm | | Nitrogen source | Free ammonia (NH₃) | Glutamine | | Activator | N-acetylglutamate | — | | Pathway | Nitrogen disposal | Nucleotide synthesis | **High-Yield:** CPS I deficiency is the most common urea cycle disorder and presents with hyperammonemia and neurological symptoms. **Clinical Pearl:** N-acetylglutamate (NAG) is the allosteric activator of CPS I; its depletion leads to secondary urea cycle dysfunction.