1-Halo analogs of dihydroxyacetone 3-phosphate. The effects of the fluoro analog on cytosolic glycerol-3-phosphate dehydrogenase and triosephosphate isomerase.
Fluoro-o-hydorxyacetone phosphate (fluoroacetol phosphate) has been prepared by oxidation of 1-fluoro-3-chloro-2-propanol to 1-fluoro-3-chloroacetone, phosphorylation with silver dibenzylphosphate, and the intermediate isolation of 1-fluoro-3-hydroxyacetone phosphate dibenzyl ester, followed by catalytic hydrogenation and preparation of the stable monosodium salt. The chloro analog as the pure, stable monosodium salt has been prepared by a similar route from 1,3-dichloroacetone. 1-Fluoro-3-hydroxyacetone-P is substrate for cytosolic NAD+-linked glycerol-3-P dehydrogenese (EC 1.1.1.8) from rabbit skeletal muscle with an apparent Km of 50 mM under conditions in which dihydroxyacetone-P exhibits an apparent Km of 0.15 mM. Under these conditions the fluoro analog is 85% hydrated wheras dihydroxyacetone-P has been shown by others to be 44% hydrated. The turnover numbers are 49,000 molecules of NADH oxidized per minute per molecule of enzyme at 25 degrees with the fluoro analog as substrate, and 60,000 with dihydrocyacetone-P as substrate. The product of the reduction of the fluoro analog has been identified as 1-fluorodeoxyglycerol-3-P. 1-Fluoro-3-hydroxyacetone-P is comparatively weak irreversible inhibitor at 4 degrees of rabbit muscle triosephosphate isomerase (EC 5.3.1.1) with second-order rate constant of 2.6 M minus 1 sec minus 1. Inhibition by pyrazole in vivo of alcohol dehydrogenese catalyzed oxidation of 1-fluorodeoxyglecerol-3-P indicates in mice the reduction of 1-fluoro-3-hydroxyacetone-P to -l-1-fluorodexoxyglycerol-3-P  is not significant metabolic route, or that an alternative route exists when the alcohol dehydrogenase dependent pathway is inhibited.
D000818:Animals; D001966:Bromine; D002238:Carbohydrate Epimerases / Q000378:metabolism*; D002713:Chlorine; D003600:Cytosol / Q000201:enzymology; D004099:Dihydroxyacetone Phosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005461:Fluorine; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009132:Muscles / Q000201:enzymology; D011817:Rabbits; D013329:Structure-Activity Relationship; D014305:Triose-Phosphate Isomerase / Q000378:metabolism*; D014306:Trioses / Q000031:analogs & derivatives*
D014306:Trioses; D005461:Fluorine; D002713:Chlorine; D004099:Dihydroxyacetone Phosphate; D005993:Glycerolphosphate Dehydrogenase; D002238:Carbohydrate Epimerases; D014305:Triose-Phosphate Isomerase; D001966:Bromine