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 natural and synthetic inhibitor of cystathionine gamma-lyase) was isolated from liver of rats intraperitoneally administered D,L-propargylglycine with ion-exchange chromatography, and identified as a glutathione analogue, N-[N-gamma-glutamyl(propargylglycyl)]glycine (gamma-Glu-PPG-Gly), by fast-atom-bombardment-mass spectrometry and reactions of the compound 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-propargylglycine. When the dose of D,L-propargylglycine was 50 mg/kg of body weight, 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 maximum level of gamma-Glu-PPG-Gly at 8 h was 1.15 +/- 0.08 micromol/g of liver. The propargylglycine moiety of gamma-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 gamma-Glu-PPG-Gly is a major intermediate of propargylglycine metabolism in rat liver. The structural resemblance between glutathione and gamma-Glu-PPG-Gly suggests a possible involvement of propargylglycine and gamma-Glu-PPG-Gly as cysteine and glutathione analogues, respectively, in sulfur amino-acid metabolism.
Ohta
J
J
Department of Biochemistry, Okayama University Medical School, Shikatacho, Japan.
Ubuka
T
T
Kodama
H
H
Sugahara
K
K
Nagamine
N
N
D000480:Alkynes / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D006868:Hydrolysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar
D000480:Alkynes; C105146:gamma-glutamylpropargylglycylglycine; C009055:propargylglycine; D005978:Glutathione; D005998:Glycine