Category: biosynthesis
Hepatic mitochondrial → cytosolic cycle converting two molecules of toxic NH3 into one neutral urea. Mitochondrial: NH3 + CO2 → carbamoyl phosphate (CPS1, rate-limiting, N-acetylglutamate-activated) → citrulline (OTC). Cytosolic: citrulline + aspartate → argininosuccinate (ASS1) → arginine + fumarate (ASL) → urea + ornithine (arginase). Ornithine re-enters mitochondria. Genetic defects in OTC (X-linked) and CPS1 are the most common urea-cycle disorders — present as hyperammonemic encephalopathy.