The Effect of the Administration of L-Tryptophan on Synthesis of Urea and Gluconeogenesis in Man

Abstract
Inhibition of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) after L-. tryptohan administration has previously been indicated in animal experiments. To see if a similar phenomenon would be detected in man and if such an inhibition would result in decreased glucose and urea production by the liver, experiments were performed with 3 healthy subjects. Tryptophan was given by stomach tube located in the duodenum to 3 volunteers kept on a carbohydrate-free diet for 3 days. On the 4th day a mixture of L-amino acids was infused continuously for 3 hours. Glucose and urea production from the liver were found to be decreased following tryptophan administration. Concurrent measurements of pyruvate, lactate, α-ketoglutarate, acetoacetate, ß-hydroxybutyrate, aspartate and glutamate in arterial and liver vein blood indicated that phosphoenolpyruvate carboxykinase was inhibited. This inhibition was judged to be the direct cause of the reduction in glucose production and indirectly the cause for the fall in urea production.