argininosuccinate

Argininosuccinate is the anion of argininosuccinic acid, an intermediate in both the urea cycle and arginine biosynthesis. In mammals it is produced from citrulline and aspartate by the enzyme argininosuccinate synthetase, a reaction that consumes ATP. It is subsequently cleaved by argininosuccinate lyase to yield arginine and fumarate. This sequence links nitrogen disposal with the supply of fumarate to the citric acid cycle.

In humans and other mammals, the urea cycle occurs primarily in the liver and, to a lesser extent, in the kidney. Argininosuccinate serves as a critical branching point: its breakdown provides arginine, a semi-essential amino acid used for protein synthesis and generation of several biomolecules, and fumarate, which feeds into the citric acid cycle. In many microorganisms and plants, a parallel arginine biosynthesis pathway uses the same intermediates, including argininosuccinate, to construct arginine rather than disposing of excess nitrogen.

Clinical significance arises from disruptions in the enzymes that metabolize argininosuccinate. Deficiency of argininosuccinate lyase leads to argininosuccinic aciduria (also known as argininosuccinate lyase deficiency), a urea cycle disorder characterized by accumulation of argininosuccinate and hyperammonemia. Diagnosis often involves elevated argininosuccinate levels in blood or urine and newborn screening. Management focuses on controlling ammonia levels and supporting overall metabolic health, sometimes including dietary protein restriction and medical therapies.

Argininosuccinate therefore occupies a pivotal role in nitrogen metabolism, connecting amino acid synthesis with energy production and nitrogen disposal across diverse organisms.