Formation of gamma-glutamylpropargylglycylglycine from propargylglycine inhuman blood and erythrocytes

gamma-Glutamylpropargylglycylglycine (gamma-Glu-PPG-Gly) was isolated as a metabolite of propargyl-glycine (2-amino-4-pentynoic acid, a natural and sy nthetic inhibitor of cystathionine gamma-lyase) from human blood incubated with D,L-propargylglycine in the presence of L-glutamate and glycine, and i dentified by fast-atom-bombardment mass spectrometry, indicating that human blood can metabolize propargylglycine to gamma-Glu-PPG-Gly. When whole blo od was incubated with 2mM D,L-propargylglycine in the presence of 10 mM L-g lutamate and 10 mM glycine at 37 degrees C for 16 h, 0.094 +/- 0.013 mu mol of gamma-Glu-PPG-Gly was formed per mi of whole blood. When erythrocytes w ere incubated under the same conditions for 16 h, 0.323 +/- 0.060 mu mol of gamma-Glu-PPG-Gly was formed per mi of erythrocytes, suggesting a large co ntribution of erythrocytes to gamma-Glu-PPG-Gly formation in whole blood. T he apparent K-m 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-Gl y formation and the K-m value for D,L-propargylglycine suggest that metabol ism of propargylglycine to gamma-Glu-PPG-Gly can play a definite biological role in human subjects who are loaded with propargylglycine.