Fluorine-containing analogues of intermediates in the Shikimate pathway.
The phosphoenolpyruvate analogue (Z)-phosphoenol-3-fluoropyruvate is a substrate for phenylalanine-inhibitable 3-deoxy-D-arabino-heptulosonic acid-7-phosphate synthase from Escherichia coli. In the presence of excess erythrose 4-phosphate, apparent KM values of 65 and 38 muM were observed for phosphoenol-3-fluoropyruvate and phosphoenolpyruvate, respectively. Because the apparent Vmax for phosphoenol-3-fluoropyruvate is only 1.17% of that for phosphoenolpyruvate, one can study the former as an inhibitor of 3-deoxy-arabino-heptulosonic acid-7-phosphate synthase. Kinetic experiments showed phosphoenol-3-fluoropyruvate to be competitive with respect to phosphoenolpyruvate. Two distinguishable Ki values of 8 and 48 muM were obtained. The product (3S)-3-deoxy--3-fluoro-arabino-heptulosonic acid 7-phosphate was purified, characterized, and shown to act as a substrate for 5-dehydroquinate synthase. 3-Deoxy-3-fluoro-arabino-heptulosonic acid 7-phosphate, in contrast to 3-deoxy-arabino-heptulosonic acid 7-phosphate reacts slowly or not at all with reagents specific for 2-keto-3-deoxy sugars and is relatively resistant to oxidative cleavage by sodium periodate. The expected product of periodate oxidation, 3-fluoro-3-formylpyruvate, cannot be detected. This observation was clarified by studies with model compounds.
D010723:3-Deoxy-7-Phosphoheptulonate Synthase / Q000378:metabolism*; D000446:Aldehyde-Lyases / Q000378:metabolism*; D004926:Escherichia coli; D005461:Fluorine; D007700:Kinetics; D010504:Periodic Acid / Q000494:pharmacology; D010728:Phosphoenolpyruvate / Q000031:analogs & derivatives* / Q000378:metabolism; D012765:Shikimic Acid / Q000378:metabolism*; D013780:Tetroses / Q000378:metabolism
D013780:Tetroses; D010504:Periodic Acid; D005461:Fluorine; D012765:Shikimic Acid; D010728:Phosphoenolpyruvate; D010723:3-Deoxy-7-Phosphoheptulonate Synthase; D000446:Aldehyde-Lyases