TRANSAMINATION OF METHIONINE AFTER LOADING IN PATIENTS WITH CIRRHOSIS

Background/Aims: An impaired methionine degradation along the transsul furation pathway has been widely described in cirrhosis. Evidence has been provided that methionine can also be degraded via a transaminatio n pathway, leading to formation of methanethiol and its metabolites, p rotein-S-SCH3 (a mixed disulphide of blood proteins and methanethiol), alpha-ketomethylthiobutyrate and X-S-SCH3 (a mixed disulphide of a th iol with an unknown component X and methanethiol). This pathway seems to be of little importance in normal subjects, even after methionine l oading, but its role in the presence of an acquired transsulfuration d efect has never been tested. Methods: We measured the plasma concentra tion of methanethiol metabolites in six normal subjects and 11 patient s with cirrhosis receiving a primed-continuous infusion of L-methionin e, at rates able to increase plasma methionine to levels approximately 20 times basal concentrations. Results: Before methionine infusion, t he sum of transamination metabolites was similar in the two groups (0. 29+/-SD 0.07 mu mol/l in controls and 0.45+/-SD 0.22 in patients with cirrhosis). During methionine infusion and after the end of infusion, there was a progressive increase of transamination metabolites, which reached values approximately 10 times basal concentrations, with no di fference between groups. Conclusions: We conclude that transamination cannot represent a quantitatively important exit for excess methionine in subjects with cirrhosis, in the presence of an acquired block alon g the transsulfuration pathway.