Arginiosuccinate

Argininosuccinate, also called argininosuccinic acid in its acid form and commonly referred to as argininosuccinate in the urea cycle, is a key intermediate in nitrogen disposal. It is formed in the liver cytosol by the ATP-dependent condensation of citrulline with aspartate, catalyzed by argininosuccinate synthetase. Argininosuccinate is then cleaved by argininosuccinase to yield arginine and fumarate. The fumarate can enter the citric acid cycle, linking nitrogen excretion with energy metabolism, while arginine serves as a substrate for urea production.

Chemically, argininosuccinate is a polar, dianionic molecule at physiological pH. It exists in solution as a hydrated, highly soluble intermediate and does not cross cell membranes readily, reflecting its role as an intracellular metabolite within the urea cycle.

Clinical significance of argininosuccinate arises mainly through defects in the enzymes of its formation and breakdown. Argininosuccinate lyase deficiency (ASL deficiency) causes argininosuccinic acidemia, with elevated argininosuccinate in plasma and urine and can present with hyperammonemia, liver dysfunction, and developmental delay. Argininosuccinate synthetase deficiency (ASS1 deficiency) leads to citrullinemia type I, in which citrulline accumulates and ammonia may rise due to impaired production of argininosuccinate. Measurement of argininosuccinate levels in blood or urine is used, alongside other amino acids, in the diagnosis and monitoring of urea cycle disorders. Management focuses on reducing ammonia levels and maintaining metabolic balance through diet and medical therapy.

Synonyms include argininosuccinate and argininosuccinic acid; the term argininosuccinate is widely used in English-language biomedical literature.