Studies on the biochemical basis of distal axonopathies. I. Inhibition of glycolysis by neurotoxic hexacarbon compounds

M. I. Sabri, C. L. Moore, Peter Spencer

Research output: Contribution to journalArticle

78 Citations (Scopus)

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 MnBK 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.

Original languageEnglish (US)
Pages (from-to)683-689
Number of pages7
JournalJournal of Neurochemistry
Volume32
Issue number3
StatePublished - 1979
Externally publishedYes

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Glyceraldehyde-3-Phosphate Dehydrogenases
Glycolysis
Methyl n-Butyl Ketone
Enzyme inhibition
Axonal Transport
Dithiothreitol
Neurotoxins
Enzyme activity
Enzymes
Acetone
L-Lactate Dehydrogenase
Energy Metabolism
Crystalline materials

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Studies on the biochemical basis of distal axonopathies. I. Inhibition of glycolysis by neurotoxic hexacarbon compounds. / Sabri, M. I.; Moore, C. L.; Spencer, Peter.

In: Journal of Neurochemistry, Vol. 32, No. 3, 1979, p. 683-689.

Research output: Contribution to journalArticle

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