Effect of hydrazine on urea cycle enzymes in vitro and in vivo

Abstract

The effect of hydrazine on urea cycle enzymes was studied in adult male rats. Addition of different concentrations of hydrazine to homogenates of rat liver produced a gradual inhibition of citrulline and urea synthesis. A daily injection of subconvulsive doses (32 mg/kg) of this toxic substance for 4 days provoked an increase of citrulline and urea contents in different tissues. The activities of urea cycle enzymes were not affected by such a treatment except for argininosuccinase where an increase was noted. The activity of ornithine-ketoacid transaminase was greatly inhibited. The results suggest that the inhibition of ornithine-ketoacid transaminase provokes an accumulation of ornithine. The presence of a high concentration of this amino acid together with an increased ammonia production stimulates urea synthesis. Under these physiological conditions, the condensation reaction of citrulline with aspartic acid may become ratelimiting in the operation of the urea cycle with the resultant accumulation of citrulline.