Synthesis of glutathione in response to methionine load in control subjects and in patients with cirrhosis

The fasting plasma level of reduced glutathione (GSH), a methionine-derived tripeptide, is reduced in cirrhosis, There is evidence that a reduced acti vity of S-adenosyl-L-methionine synthetase limiting the flux of methionine along the transmethylation/transsulfuration pathway may contribute to decre ase GSH levels. Mo studies have analyzed plasma GSH in response to a methio nine load. In 6 control subjects and in 10 patients with cirrhosis, plasma sulfur amino acid and plasma and erythrocyte GSH levels were measured in re sponse to a L-methionine load (0.1 g/kg). Blood samples were obtained throu ghout the day after the oral load. Urine was collected for measurement of s ulfur excretion. During the study period, all subjects consumed a standard diet of 1,683 kcal containing 2% protein and virtually no methionine, Plasm a methionine increased in both groups to a peak level exceeding 20 times th e basal value 90 minutes after the load, and declined thereafter. Methionin e clearance, calculated on the descending part of the methionine-time curve , was reduced by 50% in cirrhosis (P = .0001), Pasting GSH was higher in co ntrols (mean +/- SD, 3.9 +/- 1.3 v 1.6 +/- 0.7 mu mol/l P = .0004). In resp onse to a methionine load, it peaked at 10.2 +/- 7.2 and 3.2 +/- 1.3 mu mol /L, respectively (P = .009). Thereafter, plasma GSH progressively declined, and after 24 hours, it returned to the fasting preinfusion values in both groups. Plasma cysteine and taurine concentrations, as well as the erythroc yte GSH time course, paralleled plasma GSH levels, with less significant di fferences between groups. Sulfate excretion was delayed. GSH synthesis is s timulated by a methionine load. The reduced flux of methionine along the tr ansmethylation/transsulfuration pathway reduces GSH synthesis in cirrhosis. Defective methionine metabolism also may he responsible for reduced fastin g GSH. Copyright (C) 2000 by W.B. Saunders Company.