The relationship between the formation of urea and argininosuccinate in a patient with argininosuccinic aciduria studied with labelled precursors.

1. The time-course of urinary excretion of [15N]urea and [lSN]argininosuccinate or [''Nlarginine after an oral dose of [15N]ammonium lactate has been followed in patients with argininosuccinic aciduria and cystine-lysinuria respectively. The labelled argininosuccinate and arginine appeared more slowly than expected on simple precursor-product models. 2. In the patient with argininosuccinic aciduria, simultaneous ingestion of ['"Iammonium lactate and [carbam~yl-~~C]citrulline gave very different ratios of labelling with the two isotopes for urinary urea and argininosuccinate. Urinary argininosuccinate had not been in equilibrium with the urea precursor in this patient, but the plasma [' 4C]citrulline bore a reasonable precursor-product relationship to the urinary ['4C]argininosuccinate. 3. Intravenous [g~anidino-~~C]arginine giv n to the patient with argininosuccinic aciduria resulted in a much higher degree of labelling of the plasma globulins than the albumin. This is consistent with a considerable turnover of hepaticarginine, as would be expected with a functioning Krebs-Henseleit urea cycle. 4. These results can be explained with a compartmentation model in which most of the urea is synthesized in the liver, but most of the urinary argininosuccinate is peripheral in origin.