Argininosuccinate synthase

Argininosuccinate synthase (ASS1) is a 412-amino acid enzyme that catalyzes the condensation of aspartate, citrulline, and ATP to form argininosuccinate, a key step in both the urea cycle and arginine biosynthesis (UniProt: P00966). The enzyme detoxifies ammonia produced during protein catabolism by converting it to urea in the liver, while also supplying arginine to most body tissues. Loss-of-function mutations cause citrullinemia type 1 (CTLN1, MIM 215700), an autosomal recessive urea cycle disorder presenting with hyperammonemia, seizures, and developmental encephalopathy.

In Alzheimer's disease brain tissue, ASS1 is upregulated relative to age-matched controls (mean log2 fold-change +1.35; Chaparral AD proteomics), based on quantitative proteomics of post-mortem human brain across multiple subcellular fractions. This upregulation may reflect altered ammonia metabolism or increased arginine demand in the context of neurodegeneration, though the functional significance in AD pathogenesis requires further investigation. No additional disease associations are currently curated for this protein.