Formation of gamma-glutamylpropargylglycylglycine from propargylglycine in human blood and erythrocytes.
Gamma-Glutamylpropargylglycylglycine (gamma-Glu-PPG-Gly) was isolated as a metabolite of propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine gamma-lyase) from human blood incubated with D,L-propargylglycine in the presence of L-glutamate and glycine, and identified by fast-atom-bombardment mass spectrometry, indicating that human blood can metabolize propargylglycine to gamma-Glu-PPG-Gly. When whole blood was incubated with 2 mM D,L-propargylglycine in the presence of 10 mM L-glutamate and 10 mM glycine at 37 degrees C for 16h, 0.094+/-0.013 micromol of gamma-Glu-PPG-Gly was formed per ml of whole blood. When erythrocytes were incubated under the same conditions for 16h, 0.323+/-0.060 micromol of gamma-Glu-PPG-Gly was formed per ml of erythrocytes, suggesting a large contribution of erythrocytes to gamma-Glu-PPG-Gly formation in whole blood. The apparent Km value of gamma-Glu-PPG-Gly formation in human erythrocytes for D,L-propargylglycine was 0.32 mM. The observed rate of gamma-Glu-PPG-Gly formation and the Km value for D,L-propargylglycine suggest that metabolism of propargylglycine to gamma-Glu-PPG-Gly can play a definite biological role in human subjects who are loaded with propargylglycine.
Nagamine
N
N
Department of Biochemistry, Okayama University Medical School, Japan.
Ohta
J
J
Masuoka
N
N
Kodama
H
H
Ubuka
T
T
D000328:Adult; D000480:Alkynes / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000302:isolation & purification; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D008875:Middle Aged; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000480:Alkynes; C105146:gamma-glutamylpropargylglycylglycine; C009055:propargylglycine; D005978:Glutathione; D005998:Glycine