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-MI; Ederle-K; Holdsworth-CE; Spencer-PS
Neurotoxicology 1979 Jan; 1(2):285-297
The effects of 2,5-hexanedione (110134) (2,5-HD) and methyl-n-butyl- ketone (591786) (MnBK) on phosphofructokinase (PFK) activity were examined. Activities of PFK in brain homogenates were also determined in animals chronically intoxicated with 5 percent 2,5-HD in their drinking water for 10 to 12 weeks. Lactic dehydrogenase (LDH) activity was studied for comparison. The neurotoxic hexacarbon compounds 2,5-HD and MnBK inhibited PFK activity in pure crystalline form and in brain homogenates. 2,5-HD was considerably more inhibitory than MnBK. LDH activity was unaffected both in- vitro and in-vivo. PFK activity was also reduced in brain homogenates obtained from the chronically intoxicated rats. The authors conclude that neurotoxic hexacarbon compounds inhibit the activity of enzymes required for energy production and maintenance of nerve fiber integrity.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Industrial-organic-chemicals; In-vitro-study; Neurotoxins; Enzyme-activity; Enzymatic-inhibition; Biochemical-effects; Biochemical-reactions
Pathology Albert Einstein Coll of Med 1300 Morris Park Avenue Bronx, N Y 10461
Neurotoxic Disorders; Neurotoxic-effects
Yeshiva University, New York, New York