A ¹⁵N GC/MS Study of in Vivo Glutamine Synthesis in Liver Failure Rats

To clarify the nature of nitrogen metabolism between branched chain amino acid (BCAA) and glutamine (GIn) in liver failure, we measured arterial plasma concentrations of GIn and ¹⁵N uptake to amino-N and amide-N of GIn in normal and D-galactosamine-induced fulminant hepatic failure (FHF) rats after ¹⁵N-leucine (Leu) injection. Fifteen, 30 and 60 min after Leu injection, the arterial plasma concentrations of GIn were significantly higher in FHF rats than in controls. The concentrations of amino-¹⁵N GIn were also significantly higher in FHF rats than in controls at 5, 15, 30 and 60 min after injection. The concentrations of amide-¹⁵N GIn did not significantly differ between FHF and controls at 5, 15 and 30 min. However, at 60 min, the concentration was significantly higher in the FHF rats. The higher uptake of ¹⁵N to amino-N of GIn in FHF rats suggests the presence of an enhanced ability to synthesize GIn from Leu in FHF rats. The higher uptake of ¹⁵N to amide-N of GIn in FHF rats at 60 min after injection suggests that excessive administration of BCAA to patients with severely impaired urea-cycle capacity suffering with hepatic failure may lead to greater levels of hyperammonemia.