A new metabolite of propargylglycine, γ-glutamylpropargylglycylglycine, in liver of D,L-propargylglycine-administered rats

A new metabolite of propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine γ-lyase) was isolated from liver of rats intraperitoneally administered D,L-propargylglycine with ion-exchange chromatography, and identified as a glutathione analogue, N-[N-γ-glutamyl(propargylglycyl)]glycine (γ-Glu-PPG-Gly), by fast-atom-bombardment-mass spectrometry and reactions of the compound including acid hydrolysis, carboxypeptidase reaction, and γ-glutamyltranspeptidase reaction. The content of γ-Glu-PPG-Gly in rat liver increased dose-dependently with the increase of D,L-propargylglycine. When the dose of D,L-propargylglycine was 50 mg/kg of body weight, the increase of γ-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 maximum level of γ-Glu-PPG-Gly at 8 h was 1.15 ± 0.08 μmol/g of liver. The propargylglycine moiety of γ-Glu-PPG-Gly in rat liver at 14 h after the administration of D,L-propargylglycine corresponded to 2-7% of the propargylglycine administered when the dose of D,L-propargylglycine was 3.125-200 mg/kg of body weight. The present results indicate that γ-Glu-PPG-Gly is a major intermediate of propargylglycine metabolism in rat Liver. The structural resemblance between glutathione and γ-Glu-PPF-Gly suggests a possible involvement of propargylglycine and γ-Glu-PPG-Gly as cysteine and glutathione analogues, respectively, in sulfur amino-acid metabolism.