Transamination of methionine after loading in patients with cirrhosis.
OBJECTIVE
An impaired methionine degradation along the transsulfuration pathway has been widely described in cirrhosis. Evidence has been provided that methionine can also be degraded via a transamination pathway, leading to formation of methanethiol and its metabolites, protein-S-SCH3 (a mixed disulphide of blood proteins and methanethiol), alpha-ketomethylthiobutyrate and X-S-SCH3 (a mixed disulphide of a thiol with an unknown component X and methanethiol). This pathway seems to be of little importance in normal subjects, even after methionine loading, but its role in the presence of an acquired transsulfuration defect has never been tested.


METHODS
We measured the plasma concentration of methanethiol metabolites in six normal subjects and 11 patients with cirrhosis receiving a primed-continuous infusion of L-methionine, at rates able to increase plasma methionine to levels approximately 20 times basal concentrations.


RESULTS
Before methionine infusion, the sum of transamination metabolites was similar in the two groups (0.29 +/- SD 0.07 mumol/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 difference 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 along the transsulfuration pathway.
Bugianesi
E
E
Istituto di Clinica Medica Generale e Terapia Medica, University of Bologna, Italy.
Tangerman
A
A
Ronchi
M
M
Bianchi
G
G
Marchesini
G
G
D005690:Galactose / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; C005231:methylmercaptan; D008715:Methionine; D005690:Galactose