In vitro and in vivo inhibition of glycolytic enzymes by acrylamide

The effect of acrylamide on glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, and lactate dehydrogenase has been studied both in vitro and in vivo. Acrylamide inhibited crystalline GAPDH and PFK from rabbit muscle as well as the enzyme present in rat brain and sciatic nerve homogenates in vitro. Inhibition of enzyme activity was a function of the concentration and the duration of preincubation with acrylamide. Enzyme inhibition was prevented by dithiothreitol. Acrylamide did not inhibit LDH activity even at high concentrations. Rats intoxicated with acrylamide had approximately 33% less GAPDH in sciatic nerves, but normal levels were found in liver and brain homogenates. The significance of selective GAPDH inhibition is discussed in relation to the pathogenesis of peripheral neuropathy induced by acrylamide.