How does the urea cycle work step by step?

The urea cycle takes harmful ammonia and converts it into urea, which can be excreted safely in urine. This process happens in the liver, with steps occurring both in the mitochondria and the cytoplasm. The cycle involves five main stages:

1. Carbamoyl phosphate synthesis- In the mitochondria, the enzyme carbamoyl phosphate synthetase I (CPS I) uses ammonia ((NH3), bicarbonate ((HCO-3), and two molecules of ATP to form carbamoyl phosphate.
2. Citrulline formation- Carbamoyl phosphate combines with ornithine in a reaction catalyzed by ornithine transcarbamylase (OTC), forming citrulline. Citrulline is then transported out of the mitochondria into the cytoplasm.
3. Argininosuccinate synthesis- In the cytoplasm, citrulline reacts with aspartate (which donates the second nitrogen for urea). This step, catalyzed by argininosuccinate synthetase, requires one ATP molecule and produces argininosuccinate.
4. Fumarate and arginine formation- Argininosuccinate lyase splits argininosuccinate into fumarate and arginine.
5. Urea and ornithine formation- Finally, arginase hydrolyzes arginine, releasing urea and regenerating ornithine. The urea moves to the kidneys for excretion in urine, while ornithine returns to the mitochondria to restart the cycle.