The hypoglycaemic action of tryptophan in the rat.

The results are consistent with an inhibition of gluconeogenesis at the level of phosphoenolpyruvate carboxykinase in the rat liver cells. The time-course of the large increases in intracellular malate and aspartate, and decrease in phosphoenolpyruvate, is similar to that of the decrease in glucose output by the cells. The lack of inhibition of glucose production from glycerol or D-fructose is also consistent with an inhibition of the pathway before t r i m phosphate formation. The absence of inhibition of gluconeogenesis in guinea-pig hepatocytes by 0.5 mM-Ltryptophan is yet another example of a difference between the rat and the guinea pig. There are many possible explanations for the different sensitivities to L-tryptophan. For example: (a) there may be differences in the metabolism of L-tryptophan between the two species; (b) compartmentation of metabolites may be important, in view of the differing distributions of phosphoenolpyruvate carboxykinase; and (c) the enzyme phosphoenolpyruvate carboxykinase may itself differ in its sensitivity to L-tryptophan in the two species.