Urea Cycle- Enzymes and Steps


The urea cycle is a series of biochemical reactions that produces urea from ammonia. Urea is a less toxic substance that can be excreted by the kidneys. The urea cycle is essential for animals that cannot easily and safely remove nitrogen as ammonia, such as mammals and amphibians.

The urea cycle takes place primarily in the liver, which is the main organ responsible for detoxifying ammonia and converting it to urea . However, the urea cycle is not confined to a single cellular compartment. It involves both the cytosol and the mitochondria of hepatocytes, which are the liver cells .

The first reaction of the urea cycle occurs in the mitochondria, where ammonia is converted to carbamoyl phosphate by the enzyme carbamoyl phosphate synthetase I. This reaction requires two ATP molecules and bicarbonate. Carbamoyl phosphate then reacts with ornithine, a non-protein amino acid, to form citrulline. This reaction is catalyzed by ornithine transcarbamoylase, another mitochondrial enzyme. Citrulline is then transported to the cytosol in exchange for ornithine, which re-enters the mitochondria for another round of the cycle.

The remaining three reactions of the urea cycle occur in the cytosol. Citrulline combines with aspartate, another amino acid, to form argininosuccinate. This reaction requires one ATP molecule and is catalyzed by argininosuccinate synthetase. Argininosuccinate then splits into arginine and fumarate by the action of argininosuccinate lyase. Fumarate can enter the citric acid cycle or be converted to malate and then to glucose or aspartate. Arginine is cleaved by arginase, a cytosolic enzyme, to produce urea and ornithine. Urea is then released into the blood stream and transported to the kidneys for excretion. Ornithine is transported back to the mitochondria to complete the cycle.

The urea cycle is thus partly cytoplasmic and partly mitochondrial. It involves five enzymes and four intermediates. It also interacts with other metabolic pathways, such as amino acid metabolism and citric acid cycle. The urea cycle is a vital process for maintaining nitrogen balance and preventing ammonia toxicity in animals that use this cycle.