Carbamoyl phosphate synthetase I

Definition

Carbamoyl phosphate synthetase I (CPSI) is a key enzyme in the urea cycle that catalyzes the conversion of ammonia and bicarbonate into carbamoyl phosphate, using ATP as a phosphate donor. This reaction is crucial for the detoxification of ammonia, which is produced during amino acid catabolism, making CPSI a central player in nitrogen metabolism and excretion in animals.

5 Must Know Facts For Your Next Test

1. CPSI is located in the mitochondria of liver cells, where it initiates the urea cycle by incorporating free ammonia into carbamoyl phosphate.
2. The reaction catalyzed by CPSI requires two molecules of ATP and is one of the rate-limiting steps of the urea cycle.
3. CPSI activity is regulated by N-acetylglutamate, which acts as an allosteric activator, increasing the enzyme's affinity for its substrates.
4. Deficiency in CPSI can lead to hyperammonemia, a condition characterized by elevated ammonia levels in the blood, which can cause neurological damage.
5. CPSI is distinct from carbamoyl phosphate synthetase II (CPSII), which is involved in pyrimidine biosynthesis and functions in the cytosol.

Review Questions

• How does carbamoyl phosphate synthetase I contribute to the detoxification of ammonia in the body?
  • Carbamoyl phosphate synthetase I plays a vital role in detoxifying ammonia by catalyzing its conversion into carbamoyl phosphate, which then enters the urea cycle. This process helps prevent ammonia accumulation, which can be toxic to cells. By facilitating this conversion, CPSI ensures that excess nitrogen from amino acid catabolism is safely processed and ultimately excreted as urea.
• Discuss the regulation mechanisms of carbamoyl phosphate synthetase I and their physiological significance.
  • Carbamoyl phosphate synthetase I is primarily regulated by N-acetylglutamate, an allosteric activator that enhances the enzyme's activity. This regulation is physiologically significant because it ensures that CPSI is active when there are high levels of ammonia in the liver, indicating increased protein breakdown or dietary intake. This feedback mechanism helps maintain nitrogen balance and prevents hyperammonemia, a potentially harmful condition.
• Evaluate the consequences of a deficiency in carbamoyl phosphate synthetase I on overall nitrogen metabolism and health.
  • A deficiency in carbamoyl phosphate synthetase I can have severe consequences on nitrogen metabolism, leading to hyperammonemia due to impaired conversion of ammonia to carbamoyl phosphate. The resultant increase in ammonia levels can cause neurological impairment and may lead to severe health issues such as coma or death if not managed effectively. This condition highlights the importance of CPSI not only in amino acid catabolism but also in protecting the brain and body from toxic levels of nitrogenous waste.

Related terms

Urea Cycle:

A series of biochemical reactions that occur in the liver, converting toxic ammonia into urea for excretion from the body.

Ammonia: A nitrogenous waste product formed during amino acid breakdown that must be converted to less toxic compounds for safe elimination from the body.

Nitrogen Excretion: The process by which organisms eliminate excess nitrogen, primarily in the form of urea or uric acid, to maintain nitrogen balance and prevent toxicity.