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How does the liver convert ammonia into urea?

The liver plays a crucial role in the detoxification of ammonia, a toxic byproduct of protein metabolism, by converting it into urea. This process, known as the urea cycle or the ornithine cycle, occurs primarily in the liver cells, specifically in the hepatocytes.

Step 1: Ammonia entry into the liver

Ammonia is produced in various tissues, including the intestines, muscles, and kidneys, as a result of protein breakdown. It enters the liver through the bloodstream, where it is transported in the form of ammonium ions (NH4+).

Step 2: Formation of carbamoyl phosphate

Once inside the liver cells, ammonia combines with carbon dioxide (CO2) to form carbamoyl phosphate. This reaction is catalyzed by the enzyme carbamoyl phosphate synthetase I (CPS I) and requires the input of energy in the form of adenosine triphosphate (ATP).

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Step 3: Citrulline synthesis

Carbamoyl phosphate then reacts with ornithine, an amino acid, to form citrulline. This reaction is facilitated by the enzyme ornithine transcarbamylase (OTC).

Step 4: Argininosuccinate synthesis

Citrulline is transported out of the mitochondria and into the cytoplasm of the liver cells. In the cytoplasm, citrulline combines with aspartate, another amino acid, to form argininosuccinate. This reaction is catalyzed by the enzyme argininosuccinate synthase (AS).

Step 5: Urea formation

Argininosuccinate is then cleaved by the enzyme argininosuccinase (ASL) to produce arginine and fumarate. Arginine is further hydrolyzed by the enzyme arginase to yield urea and ornithine. Urea is a non-toxic compound that can be safely transported through the bloodstream to the kidneys for excretion in urine.

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The urea cycle is a tightly regulated process, and any disruption in its enzymes or intermediates can lead to the accumulation of ammonia in the body, resulting in a condition called hyperammonemia. Hyperammonemia can have severe neurological consequences and requires prompt medical intervention.

Keywords: ammonia, enzyme, ornithine, carbamoyl, phosphate, citrulline, argininosuccinate, transported, reaction