Inhibition by hydrazine of gluconeogenesis in the rat.

Administration of hydrazine to fasted rats results in a state of hypoglycemia which slowly abates over a period of several hours. Hydrazine also abolishes the increase in blood glucose normally seen after administration of hydrocortisone to fasted rats. Comparison of the concentrations of hepatic metabolites of rats treated with hydrazine with those of control rats reveals that hydrazine causes accumulations of lactate, pyruvate, citrate, malate, and oxalacetate coincident with less than normal amounts of phosphoenolpyruvate, 2and 3-phosphoglyceric acids, and hexose monophosphates. The metabolic crossover point between oxalacetate and phosphoenolpyruvate is an indication that hydrazine in vivo inhibits the conversion of oxalacetate to phosphoenolpyruvate. Hydrazine in vifro inhibits rat liver phosphoenolpyruvate carboxykinase noncompetitively with respect to oxalacetate. Hydrazine also appears to inhibit renal gluconeogenesis. These data offer a possible explanation for the well-known hypoglycemic effect of hydrazine. Hydrocortisone is capable of increasing further the accumulations of malate and citrate in hydrazine-treated, fasted, adrenalectomized rats, whereas glucose depresses the accumulations of these same metabolites in normal rats treated with hydrazine. These observations are consistent with the known effects of hydrocortisone and glucose on gluconeogenesis and clearly demonstrate that these agents are capable of affecting reactions early in the over-ah process of the synthesis of glucose.