1-Fluoro-3-hydroxyacetone 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 a substrate for cytosolic NAD+- linked glycerol-3-P dehydrogenase (EC 188.8.131.52) 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 whereas 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° with the fluoro analog as substrate, and 60,000 with dihydroxyacetone-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 a comparatively weak irreversible inhibitor at 4° of rabbit muscle triosephosphate isomerase (EC 184.108.40.206) with a second-order rate constant of 2.6 M-1sec-1. Inhibition by pyrazole in vivo of the alcohol dehydrogenase catalyzed oxidation of 1-fluorodeoxyglycerol-3-P indicates that in mice the reduction of 1-fluoro-3-hydroxyacetone-P to L-1-fluorodeoxyglycerol-3-P is not a significant metabolic route, or that an alternative route exists when the alcohol dehydrogenase dependent pathway is inhibited.
ASJC Scopus subject areas