Hyperammonemia causes and effects — Flashcards

Flashcard 1: Hyperammonemia results in excess NH3, which depletes _____, leading to inhibition of the TCA cycle

Answer: α-ketoglutarate

Flashcard 2: In the liver, _____ may transfer a molecule of NH3 to the urea cycle, reforming α-ketoglutarate

Answer: glutamate

Flashcard 3: What is the most common urea cycle disorder? _____

Answer: Ornithine transcarbamylase (OTC) deficiency

Flashcard 4: Where does the urea cycle occur?

Answer: steps in both the cytoplasm and mitochondria

Flashcard 5: What is the rate-limiting enzyme of the Urea Cycle?

Answer: Carbamoyl phosphate synthetase I (CPS I)

Extra: CPS I is the rate-limiting enzyme of the urea cycle and is activated by N-acetylglutamate (NAG). It is located in the mitochondria.

Flashcard 6: What is the overall purpose of the urea cycle?

Answer: to get NH4+ from amino acid catabolism into an excretable form

Flashcard 7: What is the metabolic pathway and significance of Carbamoyl Phosphate Synthetase I (CPS I)?

Answer: Urea cycle (Rate-limiting step)

Extra: Activator: N-acetylglutamate (NAG) Location: Mitochondria Source of nitrogen: Ammonia (NH3)

Flashcard 8: In which pathway is ornithine transcarbamylase involved?

Answer: urea cycle

Flashcard 9: In which pathways is carbamoyl phosphate involved?

Answer: de novo pyrimidine synthesis; urea cycle

Flashcard 10: What are the key clinical and biochemical findings in Ornithine Transcarbamylase (OTC) deficiency?

Answer: X-linked recessive deficiency of ornithine transcarbamylase, leading to hyperammonemia and increased orotic acid.

Extra: - Findings: Hyperammonemia, increased orotic acid in blood/urine (carbamoyl phosphate shunted to pyrimidine synthesis), decreased BUN. - Symptoms: Tremor, slurred speech, somnolence, vomiting, cerebral edema. - Inheritance: X-linked recessive (unlike other urea cycle enzyme deficiencies, which are AR). - Treatment: Protein restriction, ammonia scavengers (sodium benzoate, phenylbutyrate).