Effect of Salicylate on Ureagenesis in Rat Liver

Summary Salicylate at 5 mM inhibited ureagenesis from NH4C1 by about 45% in rat liver slices. Salicylate also inhibited ci-trulline synthesis in isolated mitochondria. It had no direct effect on carbamyl phosphate synthetase or ornithine transcarba-mylase assayed in liver homogenates. Salicylate did not inhibit citrulline synthesis supported by exogenous ATP. Salicylate lowered the carbamyl phosphate concentration in mitochondria incubated without ornithine to minimize citrulline synthesis. Unexpectedly salicylate stimulated mitochondrial ornithine uptake. The inhibition of ureagenesis is probably due to the uncoupling of oxidative phosphorylation which depletes mitochondrial ATP which in turn impairs carbamyl phosphate synthesis.