Further observations on in vitro and in vivo effects of 2,5-hexanedione on glyceraldehyde-3-phosphate dehydrogenase.
The in vitro and in vivo effect of aliphatic diketones has been studied on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) D,L-glyceraldehyde-3-phosphate: NAD oxidoreductase (phosphorylating EC 1.2.1.12 activity). Neurotoxic diketone, 2,5-hexanedione (2,5-HD), but not 2,4-hexanedione (2,4-HD), a non-neurotoxic diketone, inhibited GAPDH in rat bran homogenate preincubated with 25 mM diketones for 20 min. If the preincubation period was increased to 2 h, approximately 25% and 55% inhibition of GAPDH activity was observed with 1 mM and 5 mM 2,5-HD respectively. The inhibition of GAPDH activity was also seen in sciatic nerves but not in the brain or liver homogenates of rats chronically intoxicated with 2,5-HD for 12 weeks. The inhibition of GAPDH by 2,5-HD appears to be selective, and thus confirms earlier data from this laboratory.
D000818:Animals; D001921:Brain / Q000201:enzymology; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D006588:Hexanones / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
D006588:Hexanones; D007659:Ketones; D009419:Nerve Tissue Proteins; C011269:2,5-hexanedione; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases