Journal of Toxicology and Environmental Health, Part A 1985-01-01

Evaluation of the inhibition of glycolytic enzymes by the neurotoxicant dimethylaminopropionitrile.

J R Froines, A J Watson

Index: J. Toxicol. Environ. Health A 16(3-4) , 469-79, (1985)

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Abstract

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).