A four-year-old boy with hyperargininaemia had increased urinary excretion of homocitrulline and homoarginine. A single oral lysine load created a marked increase in these amino acids in plasma. A daily oral lysine supplementation resulted in a remarkable urinary leakage of homocitrulline and homoarginine. These findings suggest that the patient had an enhanced synthesis of these amino acids.
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.
A 14-year-old boy with lysinuric protein intolerance had increased plasma and urinary concentrations of homocitrulline and homoarginine. The accumulation of carbamylphosphate due to depleted supply of ornithine for the urea cycle may be responsible for the enhanced synthesis of homocitrulline and homoarginine. A renal clearance study showed that the tubular transport of homoarginine in the patient was impaired. In lysinuric protein intolerance, membrane transport system for homoarginine may be defective because it is presumed that homoarginine shares a common transport system with the dibasic amino acids.
A 4-year-old boy with hyperargininaemia had an increased urinary excretion of putrescine which was exaggerated with oral ornithine supplementation. It seems unlikely that putrescine was overproduced within the gut, because a loading with a single oral dose of ornithine showed that the intestinal ornithine absorption in the patient was normal. An acceleration of extramitochondrial ornithine metabolism due to impaired mitochondrial ornithine uptake may have caused the hyperexcretion of putrescine.
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