A method was developed for evaluating the relative rate of conversion of [14C]-citrulline to [14C]arginine in vivo. By this method it was demonstrated that the conversion was almost completely abolished by functional nephrectomy, but not by functional hepatectomy. It was also demonstrated that functional nephrectomy caused a prompt increase in the citrulline concentration in the serum, while functional hepatectomy caused a rapid decrease in it. On the basis of these findings, it was concluded that the kidney was the main organ for synthesis of arginine from citrulline, which is supplied from the liver. Studies using this method also provided evidence suggesting that arginine formation from citrulline might be controlled by insulin and by negative feedback due to dietary arginine. In addition, in vivo experiments and perfusion experiments on isolated kidney showed that guanidinoacetic acid formation from citrulline was remarkable decreased in diabetic rats. Enzymological studies suggested that this decrease might be due to a change in glycine amidinotransferase [L-arginine:glycine amidinotransferase, EC 2.1.4.1] activity.

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