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

Jun Ohta, Toshihiko Ubuka, Hiroyuki Kodama, Kazunori Sugahara, Noboru Nagamine

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)240-246
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1334
Issue number2-3
DOIs
Publication statusPublished - Mar 15 1997

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Metabolites
Liver
Rats
Glutathione
Metabolism
propargylglycine
Body Weight
Cystathionine
Cathepsin A
Fast Atom Bombardment Mass Spectrometry
Sulfur Amino Acids
Carboxypeptidases
Lyases
Ion Exchange Chromatography
Chromatography
Glycine
Mass spectrometry
Cysteine
Hydrolysis
Ion exchange

Keywords

  • 2-Amino-4-pentynoic acid
  • Cysteine
  • Enzyme inhibitor
  • Glutathione analog
  • Mushroom toxin
  • Propargylglycine

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A new metabolite of propargylglycine, γ-glutamylpropargylglycylglycine, in liver of D,L-propargylglycine-administered rats. / Ohta, Jun; Ubuka, Toshihiko; Kodama, Hiroyuki; Sugahara, Kazunori; Nagamine, Noboru.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1334, No. 2-3, 15.03.1997, p. 240-246.

Research output: Contribution to journalArticle

Ohta, Jun ; Ubuka, Toshihiko ; Kodama, Hiroyuki ; Sugahara, Kazunori ; Nagamine, Noboru. / A new metabolite of propargylglycine, γ-glutamylpropargylglycylglycine, in liver of D,L-propargylglycine-administered rats. In: Biochimica et Biophysica Acta - General Subjects. 1997 ; Vol. 1334, No. 2-3. pp. 240-246.
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abstract = "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.",
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AB - 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.

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KW - Glutathione analog

KW - Mushroom toxin

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