Carbamoyl phosphate synthetase 1

Carbamoyl phosphate synthetase 1 (CPS1) is an enzyme that plays a crucial role in the urea cycle, which is essential for the detoxification of ammonia in the liver. CPS1 catalyzes the synthesis of carbamoyl phosphate from ammonia, bicarbonate, and ATP. This reaction is the first committed step in the urea cycle, which ultimately converts toxic ammonia into urea for excretion from the body.

Structure

CPS1 is a mitochondrial enzyme, meaning it is located within the mitochondria of liver cells. It is a large, multi-domain protein that requires the presence of N-acetylglutamate as an allosteric activator. The enzyme is composed of several domains that facilitate the binding of substrates and the catalysis of the reaction.

Function

The primary function of CPS1 is to initiate the urea cycle by producing carbamoyl phosphate. This compound then reacts with ornithine to form citrulline, a reaction catalyzed by ornithine transcarbamylase. The urea cycle is vital for removing excess nitrogen from the body, which is primarily generated from the breakdown of amino acids.

Regulation

CPS1 activity is regulated by the availability of its substrates and by the concentration of N-acetylglutamate, which is synthesized in response to increased levels of amino acids. This regulation ensures that the urea cycle is active when there is a need to detoxify ammonia, such as after protein-rich meals.

Clinical significance

Deficiencies in CPS1 can lead to a condition known as Carbamoyl phosphate synthetase I deficiency, a rare genetic disorder characterized by hyperammonemia, which can cause neurological damage and other severe symptoms. Early diagnosis and management are crucial for affected individuals.

Also see

• Urea cycle
• Ornithine transcarbamylase
• Hyperammonemia
• N-acetylglutamate synthase