Evaluation of the inhibition of glycolytic enzymes by the neurotoxicant dimethylaminopropionitrile.
The neurotoxic aminonitrile dimethylaminopropionitrile (DMAPN) inhibits the crystalline glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fructose-6-phosphate kinase (phosphofructokinase, PFK). Preincubation of GAPDH with the aminonitrile enhances the inhibition, indicating that the inhibition is irreversible. The overall bimolecular rate constant ki was determined to be 2.42 +/- 0.21 M-1 min-1. Dithiothreitol (DTT) partially protected the enzyme from inhibition. PFK is also inhibited by DMAPN, but the inhibition is reversible and noncompetitive with a Kl, of 2.79 X 10(-2) M. DMAPN does not inhibit lactate dehydrogenase (LDH), nor is GAPDH or PFK inhibited by 3,3'-iminodipropionitrile (IDPN).
D000629:Aminopropionitrile / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001369:Axons / Q000187:drug effects; D001665:Binding Sites; D003486:Cyanides / Q000378:metabolism / Q000633:toxicity; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D007097:Imines; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012545:Schiff Bases; D013997:Time Factors
D003486:Cyanides; D007097:Imines; D012545:Schiff Bases; D000629:Aminopropionitrile; C019348:dimethylaminopropionitrile; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010732:Phosphofructokinase-1; D004229:Dithiothreitol