The metabolism of 3-deoxy-3-fluoro-D-glucose by Locusta migratoria and Schistocerca gregaria

3-Deoxy-3-fluoro-D-glucose (3FG) administered by injection is toxic to adult Locusta migratoria or Schistocerca gregaria (LD50, 4.8 mg/g). temperature-programmed and isothermal gas chromatographic analysis of poisoned locust haemolymph reveals the presence of a fluorinated metabolite identified as 3-deoxy-3-fluoro-D-glucitol (3FGL). The enzymes responsible for the accumulation of this metabolite are located in the fat body of the insect and partially purified as aldose reductase (alditol: NADP+ 1-oxidoreductase, EC 1.1.1.21) and sorbitol dehydrogenase (L-iditol: NAD+ 5-oxidoreductase EC 1.1.1.14) 3FGL is shown to be both a competitive inhibitor of the NAD-linked sorbitol dehydrogenase with Ki 8¿x 10(-2) M as well as a substrate with Km 0.5 M. A kinetic rate equation is derived and verified to account for the kinetic duality of 3FGL. These results partially explain the toxic effects of 3FG and are consistent with the presence of a hitherto undetected sorbitol metabolism in locusts.