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.