The two major pathways metabolizing ammonia: the urea cycle (periportal), and glutamine synthesis (pericentral).

In the urea cycle: ammonia and bicarbonate form carbamoylphosphate via carbamoyl phosphate synthetase1 (CPS1). This reaction requires N-acetylglutamate (acquired via a reaction catalysed by N-acetylglutamate synthase (NAGS)), Mg²⁺ and MgATP. Carbamoylphosphate combines with ornithine in a reaction catalysed by ornithine carbamoyltransferase (OTC) to form citrulline. Citrulline is transported to the cytosol and combines with aspartate to form argininosuccinate (reaction catalysed by argininosuccinate synthetase (ASS1)). Argininosuccinate is then cleaved by argininosuccinate lyase (ASL) yielding fumarate and arginine. Arginase (ARG1) cleaves arginine, producing urea and ornithine. Urea is excreted as waste and ornithine is transported back to the mitochondria to be used in subsequent cycles of urea synthesis. In the pericentral hepatocytes, ammonia ‘escaping’ the urea cycle is metabolized to glutamine (reaction catalysed by glutamate–ammonia ligase (GLUL).