Stereochemical studies of the pyruvate kinase reaction with (Z)- and (E)-phosphoenol-alpha-ketobutyrate.
(Z)-and (E)-phosphoenol-2-ketobutyrate were synthesized. [3-2H]-2-Ketobutyrates were formed from both isomers in the pyruvate kinase reaction in 2H2O and were converted to chiral propionates. Authentic (2S)-[2-2H]propionic acid was also prepared, and the optical rotatory dispersion curves of the propionates were compared. The rotation compared with standard propionate at 240 nm of sodium (2R)-[2-2H]propionate from the Z isomer was 47% (i.e., 53% was RS), and of (2S)-[2-2H]propionate from the E isomer was 29% (i.e., 71% was RS). Protonation at C-3 of the 2 si, 3 re face of the pseudosubstrates would have yielded (2R)- and (2S)-[2-2H]propionates from the Z and E analogues, respectively. An explanation offered for the nonstereoselective protonation that occurred is dissociation of the enol from the enzyme and subsequent random protonation in solution.
D000818:Animals; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D008968:Molecular Conformation; D009132:Muscles / Q000201:enzymology; D009905:Optical Rotatory Dispersion; D010728:Phosphoenolpyruvate / Q000031:analogs & derivatives*; D011485:Protein Binding; D011770:Pyruvate Kinase / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship
C015443:phosphoenol-2-ketobutyrate; D010728:Phosphoenolpyruvate; D011770:Pyruvate Kinase