1-Halo analogs of dihydroxyacetone 3-phosphate. The effects of the fluoro analog on cytosolic glycerol-3-phosphate dehydrogenase and triosephosphate isomerase

Biochemistry. 1975 May 20;14(10):2252-8. doi: 10.1021/bi00681a033.


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 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 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bromine
  • Carbohydrate Epimerases / metabolism*
  • Chlorine
  • Cytosol / enzymology
  • Dihydroxyacetone Phosphate / analogs & derivatives*
  • Dihydroxyacetone Phosphate / chemical synthesis
  • Dihydroxyacetone Phosphate / pharmacology
  • Fluorine
  • Glycerolphosphate Dehydrogenase / metabolism*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Muscles / enzymology
  • Rabbits
  • Structure-Activity Relationship
  • Triose-Phosphate Isomerase / metabolism*
  • Trioses / analogs & derivatives*


  • Trioses
  • Fluorine
  • Chlorine
  • Dihydroxyacetone Phosphate
  • Glycerolphosphate Dehydrogenase
  • Carbohydrate Epimerases
  • Triose-Phosphate Isomerase
  • Bromine