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Following a single oral dose of 10 mg/kg of [15N]glycine, plasma [15N]glycine kinetics and urinary 15N excretion were measured in 12 cirrhosis patients and in 6 control subjects. Cirrhosis patients were divided into two groups of 6 patients with and without a history of hepatic encephalopathy designated as group II and group I, respectively. Thirty minutes after oral administration of labeled glycine, the plasma concentration of [15N]glycine was significantly higher in both cirrhosis groups than that in the control group (P less than 0.05 and P less than 0.01). The elimination constant of plasma [15N]glycine slightly decreased in group II, but not significantly. Urinary 15N excretion did not differ among the three groups, but the rate of urinary ammonia 15N in urinary 15N was significantly increased in group II (P less than 0.05). The whole-body protein flux did not differ among the three groups, but whole-body protein breakdown was significantly increased in group II cirrhosis patients (P less than 0.05). These findings indicated that the kinetics of glycine were substantially altered in severe cirrhosis patients. Because hepatic uptake and oxidation of glycine was well maintained even in group II, increased endogenous protein breakdown seemed to be responsible for hyperglycinemia and also for the negative nitrogen balance seen in this group.

Urinary 15N-ammonia and 15N-urea were measured by gas chromatography-mass spectrometry after the intravenous administration of 15N-ammonia (0.2 mumol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary 15N-nitrogen excretion as ammonia and urea was measured during the 210-min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three-compartment model using the nonlinear least-squares method. The rate of urea synthesis in control subjects was 14.1 +/- 1.2 mg/kg/hr (mean +/- S.E.M.), and in cirrhotic patients it was 11.0 +/- 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 +/- 1.5 and 8.9 +/- 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p less than 0.001). The percentage of ammonia reutilization of a given dose of 15N-ammonia was 75.9% +/- 2.4% in compensated cirrhotic patients and 82.9% +/- 3.6% in decompensated cirrhotic patients (p less than 0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p less than 0.001) and correlated positively with ammonia reutilization (p less than 0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure.