Formation of γ-glutamylpropargylglycylglycine from propargylglycine in human blood and erythrocytes

γ-Glutamylpropargylglycylglycine (γ-Glu-PPG-Gly) was isolated as a metabolite of propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine γ-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 γ-Glu-PPG-Gly. When whole blood was incubated with 2mM D,L-propargylglycine in the presence of 10 mM L-glutamate and 10 mM glycine at 37°C for 16h, 0.094 ± 0.013 μmol of γ-Glu-PPG-Gly was formed per ml of whole blood. When erythrocytes were incubated under the same conditions for 16h, 0.323 ± 0.060; μmol of γ-Glu-PPG-Gly was formed per ml of erythrocytes, suggesting a large contribution of erythrocytes to γ-Glu-PPG-Gly formation in whole blood. The apparent Km value of γ-Glu-PPG-Gly formation in human erythrocytes for D,L-propargylglycine was 0.32 mM. The observed rate of γ-Glu-PPG-Gly formation and the Km value for D,L-propargylglycine suggest that metabolism of propargylglycine to y-Glu-PPG-Gly can play a definite biological role in human subjects who are loaded with propargylglycine.