Effect of acrylamide and related compounds on glycolytic enzymes in mouse brain in vitro.
The effects of acrylamide and eight analogues on mouse brain glycolytic enzymes were studied in vitro. Most of the neurotoxic and non-neurotoxic analogues showed inhibitory effects on enolases. Their inhibitory constants, I50, for both mouse brain total enolases and purified bovine neuron specific enolase were similar for each analogue, being lowest for N,N'-methylene-bis-acrylamide and highest for methacrylamide. A neurotoxic compound, N-isopropylacrylamide, and a non-neurotoxic compound, N,N'-methylene-bis-acrylamide, showed non-competitive inhibition towards mouse brain total enolase. After preincubation of anologues in vitro for 90 min with hepatic S-9 fraction prepared from normal mice, their inhibitory potency towards brain total enolase was also seen. When the S-9 fraction was prepared from mice pretreated with phenobarbital, the inhibitory potency was not different from that of the control. After preincubation with S-9 fraction prepared from either diethyl maleate-, or piperonyl butoxide-pretreated mice the inhibitory potency was significantly greater than with non-pretreated control mice. Many of the test analogues also showed inhibition of glyceraldehyde 3-phosphate dehydrogenase activity, the highest inhibitory potency being seen with acrylamide, but no compounds inhibited phosphofructokinase.
D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D006019:Glycolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010634:Phenobarbital / Q000494:pharmacology; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors; D010882:Piperonyl Butoxide / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology
D000178:Acrylamides; D006899:Mixed Function Oxygenases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010732:Phosphofructokinase-1; D010751:Phosphopyruvate Hydratase; D010882:Piperonyl Butoxide; D010634:Phenobarbital