ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract— Neurotoxic hexacarbon compounds 2,5-hexanedione (2,5-HD) and methyl n-butyl ketone (MnBK) inhibit crystalline and endogenous CNS and PNS glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Preincubation of the enzyme with the toxin was necessary for inhibition. The enzyme activity of GAPDH was preserved by the addition of dithiothreitol in the presence of either neurotoxin. By contrast, lactate dehydrogenase (LDH) activity was not inhibited by these neurotoxic chemicals. Neurologically inactive compounds 1,6-hexanediol and acetone failed to inhibit GAPDH. The present data indicate that 2,5-HD and M “BK block energy metabolism by inhibiting glycolysis at the site of GAPDH. These observations may account for the known failure of GAPDH-dependent axonal transport and the axonal degeneration which occurs in hexacarbon neuropathy.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1979.tb04550.x