Dynamic relationship between urea and glutamine synthesis in the mechanism of ammonia detoxication: a tracer study using 15NH4Cl in fulminant hepatic failure rats

Abstract

Fulminant hepatic failure (FHF) was produced in rats with intraperitoneal injection of D-galactosamine. 15NH4Cl (50 mg/kg of body weight) was injected into the rats via the tail vein. Arterial blood was drawn before and 5, 15, 30, 60 min after the injection of 15NH4Cl. 15N-ammonia, -urea, and -glutamine (amide and amino) were determined by gas chromatography and mass spectrometry. The plasma 15N-ammonia level was higher but decreased more rapidly in the FHF rats than in the control rats. This suggests that in FHF rats, the systemic vascular pool of ammonia is enlarged and ammonia clearance from blood is increased. The incorporation of 15N into urea was significantly different between the two groups. In FHF rats, the plasma urea-15N level rose 5 min after the injection, decreased at 15 min and was elevated again up to 60 min after injection. This biphasic change suggests that in FHF rats the incorporation of 15N into the extrahepatic glutamine pool is accelerated up to 15 min and that after 30 min a larger volume of glutamine-amide-15N is transferred to the urea cycle.