Which enzyme catalyzes the first committed step of the urea cycle, converting ammonia and carbamoyl phosphate to citrulline?

Explanation

## Urea Cycle: First Committed Step **Key Point:** Ornithine transcarbamylase (OTC) catalyzes the condensation of carbamoyl phosphate (from CPS I) with ornithine to form citrulline. This is the first committed step of the urea cycle and occurs in the mitochondrial matrix. **High-Yield:** While carbamoyl phosphate synthetase I (CPS I) produces carbamoyl phosphate, this enzyme is shared with pyrimidine synthesis and is not considered the "first committed step" of urea cycle specifically. OTC is the first step unique to urea cycle. **Clinical Pearl:** OTC deficiency is the most common urea cycle disorder (~50% of cases), presenting with hyperammonemia, encephalopathy, and developmental delay in infants. ### Urea Cycle Enzyme Sequence | Step | Enzyme | Substrate | Product | Location | |------|--------|-----------|---------|----------| | 1 | CPS I | NH₃ + CO₂ + 2 ATP | Carbamoyl-PO₄ | Mitochondrial matrix | | 2 | OTC | Carbamoyl-PO₄ + Ornithine | Citrulline | Mitochondrial matrix | | 3 | Argininosuccinate synthetase | Citrulline + Aspartate | Argininosuccinate | Cytosol | | 4 | Argininosuccinate lyase | Argininosuccinate | Arginine + Fumarate | Cytosol | | 5 | Arginase | Arginine | Urea + Ornithine | Cytosol | **Mnemonic:** CrOAA — **Cr**bamoyl-PO₄, **O**rnithine → **A**rginine → **A**rgininosuccinate (remembering OTC is step 2)