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Paths of Carbon in Gluconeogenesis and Lipogenesis

IV. INHIBITION BY l-TRYPTOPHAN OF HEPATIC GLUCONEOGENESIS AT THE LEVEL OF PHOSPHOENOLPYRUVATE FORMATION
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      l-Tryptophan administered to normal or adrenalectomized rats inhibits formation of glycogen from pyruvate, aspartate, or malate and from endogenous sources under the influence of hydrocortisone, but not from glucose or glycerol. The site of inhibition was located by determining the concentration of hepatic metabolites in fasted, normal rats and in fasted, adrenalectomized rats treated with tryptophan as compared with untreated control animals. Administration of tryptophan was found to cause rapid accumulation of lactate, pyruvate, citrate, aspartate, malate, and oxalacetate to 5 to 35 times normal concentrations. Phosphoenolpyruvate and all succeeding intermediates toward glycogen were decreased to one-half of normal concentrations or less. These data indicate that, following tryptophan administration, gluconeogenesis is blocked because phosphoenolpyruvate carboxykinase is nonfunctional. The accumulation of citrate, aspartate, and especially of malate in livers of rats given tryptophan supports the proposal that these compounds are intermediates in the conversion of pyruvate to phosphopyruvate. Tryptophan is a useful tool for studying the process of gluconeogenesis.

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