title: Investigations concerning the mode of action of 3,4-dihydroxybutyl-1-phosphonate on Escherichia coli.
abstract: Experiments were performed to evaluate the ability of the enzymes of Escherichia coli involved in glycerol 3-phosphate metabolism to recognize phosphonic acid analogues of the natural substrate. Neither the catabolic membrane-bound glycerol-3-phosphate dehydrogenase nor the acyl coenzyme A: glycerol-3-phosphate acyltransferase can use 3,4-dihydroxybutyl-1-phosphnate or 2,3-dihydroxypropyl-1-phosphonate are inhibitors of the reduction of dihydroxyactone phosphate as substrates. The 4-carbon phosphonic acid analogue does not exhibit inhibitory activity for either of these enzymes. While the 3-carbon phosphonic acid analogue has no inhibitory effect upon the catabolic dehydrogenase, it does appear to have a slight but reproducible inhibitory effect on the acyltransferase. Glycerol 3-phosphate and 3,4-dihydroxybutyl-1-phosphonate by glycerol 3-phosphate:NAD (P) oxidoreductase. rac-2,3-Dihydroxypropyl-1-phosphonate does not appear to be recognized by this enzyme. The apparent K-i for snglycerol 3-phosphate is 19 muM and for D-3,4-dihydroxybutyl-1-phosphonate it is 42 muM. In addition the glycerol 3-phosphate:NAD(P) oxidoreductase catalyzes the reduction of 4-hydroxy-3-oxobutyl-1-phosphonate (apparent K-m of 182 muM), a phosphonic acid analogue of dihydroxyacetone phosphate. 3,4-Dihydroxybutyl-1-phosphonate is both a competitive inhibitor (apparent Ki of 740 muM) and a substrate (apparent K-m of 450 muM) for the CDP-diglyceride: glycerol 3 phosphate phosphatidyltransferase but it has no effect upon CDP-diglyceride:L-serine phosphatidyltransferase. The relationship ofthese in vitro studies to in vivo investigations is discussed.
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000440:Butanols / Q000378:metabolism*; D003597:Cytosine Nucleotides; D004926:Escherichia coli / Q000201:enzymology*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D063065:Organophosphonates / Q000378:metabolism*; D010712:Phosphatidic Acids; D010718:Phosphatidylserines; D010770:Phosphotransferases / Q000378:metabolism
chemical_list: D000440:Butanols; D003597:Cytosine Nucleotides; D005994:Glycerophosphates; D063065:Organophosphonates; D010712:Phosphatidic Acids; D010718:Phosphatidylserines; D005993:Glycerolphosphate Dehydrogenase; D000217:Acyltransferases; D010770:Phosphotransferases