Effect of nitrite on ureagenesis and carbohydrate metabolism in isolated rat hepatocytes

The effect of three NaNO2 concentrations (0.5, 2.0, and 5.0 mM) on 15N-ammonia utilization, ureagenesis, glucose, pyruvate and lactate formation and glycogen breakdown were studied in isolated rat hepatocytes. Nitrite failed to affect the rate of glycogenolysis as well as the lactate and pyruvate formation, but at the same time it markedly increased the glucose formation. It is concluded that the increase in the glucose formation results from the nitrite stimulation of the rate of gluconeogenesis. An increased sodium nitrite concentration caused a significant decrease in the ammonia utilization and urea synthesis; there are strong linear correlations between the nitrite concentration and the amount of utilized ammonia (r = -0.93) and the formed urea (r = -0.96). The observed lower rate of ureagenesis in the presence of nitrite resulted from the diminished incorporation of the added 15N-ammonia into urea, as well as from the diminished urea formation from endogenous nitrogen. It is concluded that the disturbances in carbohydrate and nitrogen metabolism observed in the nitrite-poisoned animals are attributed to the direct effect of nitrite on metabolism.