The effect of dietary o,p′-DDT on ureagenesis from ammonia by isolated rat hepatocytes

Abstract

Hepatocytes isolated from rats which had been fed 1000 ppm o,p′-DDT for 2 weeks and starved for 48 hr exhibited markedly reduced rates of urea synthesis and citrulline accumulation when incubated with 10 m m NH 4Cl and 10 m m ornithine. The addition of 10 m m lactate to such incubations stimulated the rate of ureagenesis by both control and DDT-treated cells to nearly the same degree but did not eliminate the difference in rates of urea synthesis between control and DDT-treated cells. The activities of carbamoylphosphate synthase, ornithine carbamoyltransferase, arginine synthetase, and arginase were similar in livers from control and DDT-treated rats. The kinetics of the stimulation of urea synthesis by exogenous ornithine were similar with hepatocytes from both control and DDT-treated rats. Mitochondria isolated from the livers of control and DDT-treated rats exhibited similar rates of citrulline synthesis from ammonia and ornithine as well as similar responses to N-acetylglutamate and 2,4-dinitrophenol. These results suggest that DDT treatment may produce alterations in the kinetic behavior of urea cycle enzymes which are not detected in the standard assays of these enzymes or DDT treatment may interfere with the intermitochondrial transport processes required during ureagenesis from ammonia.