A NEW METABOLITE OF PROPARGYLGLYCINE, GAMMA-GLUTAMYLPROPARGYLGLYCYLGLYCINE, IN LIVER OF D,L-PROPARGYLGLYCINE-ADMINISTERED RATS

A new metabolite of propargylglycine (2-amino-4-pentynoic acid, a natu ral and synthetic inhibitor of cystathionine gamma-lyase) was isolated from liver of rats intraperitoneally administered D,L-propargylglycin e with ion-exchange chromatography, and identified as a glutathione an alogue, N-[N-gamma-glutamyl(propargylglycyl)]glycine (gamma-Glu-PPG-Gl y), by fast-atom-bombardment-mass spectrometry and reactions of the co mpound including acid hydrolysis, carboxypeptidase reaction, and gamma -glutamyltranspeptidase reaction. The content of gamma-Glu-PPG-Gly in rat liver increased dose-dependently with the increase of D,L-propargy lglycine. When the dose of D,L-propargylglycine was 50 mg/kg of body w eight, the increase of gamma-Glu-PPG-Gly was proportional to the time after the administration of D,L-propargylglycine, up to 8 h, and then gradually decreased to about 50% of the maximum at 24 h, where the max imum level of gamma-Glu-PPG-Gly at 8 h was 1.15+/-0.08 mu mol/g of liv er. The propargylglycine moiety of gamma-Glu-PPG-Gly in rat liver at 1 4 h after the administration of D,L-propargylglycine corresponded to 2 -7% of the propargylglycine administered when the dose of D,L-propargy lglycine was 3.125-200 mg/kg of body weight. The present results indic ate that gamma-Glu-PPG-Gly is a major intermediate of propargylglycine metabolism in rat liver. The structural resemblance between glutathio ne and gamma-Glu-PPG-Gly suggests a possible involvement of propargylg lycine and gamma-Glu-PPG-Gly as cysteine and glutathione analogues, re spectively, in sulfur amino-acid metabolism.