What is the Urea Cycle?

In humans and mammals, almost 80% of the nitrogen is excreted in the form of urea, which is produced through a series of reactions occurring in the cytosol and mitochondrial matrix of liver cells. These reactions are collectively called the urea cycle or the Krebs-Henseleit cycle.
Ammonia is a toxic product of nitrogen metabolism, which should be removed from our body. The urea cycle or ornithine cycle converts excess ammonia into urea in the mitochondria of liver cells. The urea forms, then enters the blood stream, is filtered by the kidneys and is ultimately excreted in the urine.
The overall reaction for urea formation from ammonia is as follows:
2 Ammonia + CO2 + 3ATP ---> urea + water + 3 ADP

Steps in the Urea Cycle

The urea cycle is a series of five reactions catalyzed by several key enzymes. The first two steps in the cycle take place in the mitochondrial matrix and the rest of the steps take place in the cytosol. Thus the urea cycle spans two cellular compartments of the liver cell.
In the first step of the Krebs-Henseleit cycle, ammonia produced in the mitochondria is converted to carbamoyl phosphate by an enzyme called carbamoyl phosphate synthetase I. 

The reaction can be given as follows:
NH3 + CO2 + 2ATP → carbamoyl phosphate + 2ADP + Pi

The second step involves the transfer of a carbamoyl group from carbamoyl phosphate to ornithine to form citrulline. This step is catalyzed by the enzyme ornithine transcarbamoylase (OTC).
 
The reaction is given as follows:
Carbamoyl phosphate + ornithine → citrulline + Pi

Citrulline thus formed is released into the cytosol for use in the rest of the steps of the cycle.
The third step is catalyzed by an enzyme called argininosuccinate synthetase, which uses citrulline and ATP to form a citrullyl-AMP intermediate, which reacts with an amino group from aspartate to produce argininosuccinate. This reaction can be given as follows:
Citrulline + ATP + aspartate → argininosuccinate + AMP + PPi

The fourth step involves the cleavage of argininosuccinate to form fumarate and arginine. Argininosuccinate lyase is the enzyme catalyzing this reaction, which can be represented as follows:
Argininosuccinate → arginine + fumarate

In the fifth and last step of the urea cycle, arginine is hydrolyzed to form urea and ornithine. This is catalyzed by arginase and can be given as follows:
Arginine → urea + ornithine

The overall reaction can be given as follows:
2NH3 + CO2 + 3ATP g urea + 2ADP + AMP + PPi + 2Pi