Argininosuccinate synthetase

Argininosuccinate synthetase is an enzyme that plays a crucial role in the urea cycle, which is the metabolic pathway in liver cells responsible for the detoxification of ammonia. This enzyme catalyzes the reaction that combines citrulline and aspartate to form argininosuccinate, an important intermediate in the urea cycle.

Function

The primary function of argininosuccinate synthetase is to catalyze the condensation of citrulline and aspartate to form argininosuccinate. This reaction also involves the hydrolysis of adenosine triphosphate (ATP) to adenosine monophosphate (AMP) and pyrophosphate. The argininosuccinate is then cleaved by the enzyme argininosuccinate lyase to form arginine and fumarate, which are further metabolized in the urea cycle and the citric acid cycle respectively.

Structure

Argininosuccinate synthetase is a homotetramer, meaning it is composed of four identical subunits. Each subunit contains a domain for ATP binding and a domain for the binding of citrulline and aspartate. The enzyme is regulated by feedback inhibition, with high levels of arginine acting to decrease its activity.

Clinical significance

Deficiency in argininosuccinate synthetase is the cause of the genetic disorder known as citrullinemia, which is characterized by elevated levels of citrulline in the blood and urine. This disorder can lead to symptoms such as hyperammonemia, encephalopathy, and potentially life-threatening metabolic acidosis. Treatment typically involves dietary restriction of protein and supplementation with arginine.

See also

• Urea cycle
• Citrullinemia
• Argininosuccinate lyase