(+/-)2,3-Dihydroxypropyl dichloroacetate, an inhibitor of glycerol kinase

Of a range of glycerol analogues, (+/-)-2,3-dihydroxypropyl dichloroacetate (III) has been shown to be the most potent inhibitor of glycerol kinase in vitro. Inhibition is noncompetitive with a Ki value of 1.8 X 10(-3) M. The presence of ATP seems essential for effective inhibition of the enzyme, suggesting that the inhibitor is phosphorylated to a glycerol-3-phosphate analogue. In vivo III causes a decrease in the specific activity of liver glycerol kinase and produces a dose-dependent reduction in blood glucose levels. There is a reduction in the conversion of [U-14C] glycerol into glucose after administration of III to CBA/CA mice while gluconeogenesis from fructose is increased. This suggests that of the enzymes of gluconeogenesis only glycerol kinase is inhibited by III. This compound may be useful in reducing the lipid contribution to gluconeogenesis in advancing cancer.