Studies on the biochemical basis of distal axonopathies. II. Specific inhibition of fructose-6-phosphate kinase by 2,5-hexanedione and methyl-butyl ketone

M. I. Sabri, K. Ederle, C. E. Holdsworth, Peter Spencer

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The effects of neurotoxic hexacarbon compounds on crystalline and nervous tissue fructose-6-phosphate kinase (phosphofructokinase, ATP:D-fructose-6-phosphate-1-phosphotransferase; E.C. No. 2.7.1.11; PFK) have been examined to illuminate the biochemical basis of axonal degeneration in toxic neuropathies. The neurotoxic hexacarbon solvent 2,5-hexanedione (2,5-HD), and to a lesser extent methyl n-butyl ketone, inhibited PFK activity in crystalline form and in normal brain homogenates, but failed to affect lactic dehydrogenase activity. Hexacarbon inhibition of PFK was prevented by prior exposure to dithiothreitol (DTT), but DTT could not restore enzyme activity once inhibited. PFK activity was also reduced in brain homogenates obtained from rats chronically intoxicated for 10-12 weeks with a drinking solution of 0.5 percent 2,5-HD. Non-neurotoxic 2,4-hexanedione had no effect on PFK activity. The results are consistent with the hypothesis that neurotoxic hexacarbon compounds inhibit the activity of enzymes required for energy production and maintenance of nerve fiber integrity.

Original languageEnglish (US)
Pages (from-to)285-297
Number of pages13
JournalNeuroToxicology
Volume1
Issue number2
StatePublished - 1979
Externally publishedYes

Fingerprint

Hexanones
Phosphofructokinase-2
Dithiothreitol
Brain
Methyl n-Butyl Ketone
Phosphofructokinase-1
Crystalline materials
Nerve Tissue
Phosphofructokinases
Poisons
Enzyme activity
Enzymes
Nerve Fibers
Drinking
Rats
Oxidoreductases
Milk
Phosphotransferases
Maintenance
Tissue

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Toxicology

Cite this

Studies on the biochemical basis of distal axonopathies. II. Specific inhibition of fructose-6-phosphate kinase by 2,5-hexanedione and methyl-butyl ketone. / Sabri, M. I.; Ederle, K.; Holdsworth, C. E.; Spencer, Peter.

In: NeuroToxicology, Vol. 1, No. 2, 1979, p. 285-297.

Research output: Contribution to journalArticle

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