ASS1 and citrullinemia: Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme in the conversion of citrulline to arginine in the urea cycle.8 As arginine is a semi-essential amino acid, the loss of ASS1 makes cells dependent on extracellular sources of arginine for survival, a state referred to as arginine auxotrophy.9 In patients, this deficiency has grave consequences, as clearly demonstrated by the childhood disease, called citrullinemia.