Inhibitory effect of intravenous lysine infusion on urea cycle metabolism

Intravenous infusion of 0.5 mmol/kg L-lysine monohydrochloride was performed in six normal volunteer subjects aged 10-14 years to study the inhibitory effect of lysine on urea cycle metabolism. The lysine infusion resulted in a significant increase in plasma levels of arginine and ornithine, and in urinary homocitrulline, putrescine, and orotic acid, accompanied by a significant increase in blood ammonia. There was little change in plasma urea and citrulline. The increase in plasma arginine appears to reflect an inhibited arginase activity although the plasma urea level did not change. The increased homocitrulline excretion suggests that ornithine conversion to citrulline via ornithine transcarbamylase (OTC) was inhibited. The simultaneous increase in plasma ornithine and urinary putrescine may reflect an inhibition of mitochondrial ornithine transport. In addition to the direct ammoniagenic property of lysine, impaired ornithine conversion to citrulline resulting from the inhibition of both OTC activity and mitochondrial ornithine uptake by lysine may be responsible for the increase in blood ammonia and urinary orotic acid. Despite the retarded citrulline formation, a promoted efflux of citrulline from mitochondria may have kept the plasma citrulline level unchanged.