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  • Title: 2,5-Hexanedione inhibits rat brain acetylcholinesterase activity in vitro.
    Author: Pereira ME, Adams AI, Silva NS.
    Journal: Toxicol Lett; 2004 Feb 02; 146(3):269-74. PubMed ID: 14687764.
    Abstract:
    A number of C(4)-C9 aliphatic ketones, including 2,5-hexanedione (2,5-HD), are acetylcholinesterase (AChE; EC 3.1.1.7) inhibitors. In the previous work, we demonstrated that antinociception induced by 2,5-HD was partially reversed by atropine. Since cholinergic system seems to be affected by hexacarbon compounds, in the present study we examined the effect of 2,5-HD on AChE activity of rat brain in vitro. The results demonstrated that both Km and Vmax were altered by 2,5-HD. At 5 mM 2,5-HD, there were no significant changes in Km or Vmax parameters, but at concentrations higher than 10 mM an increase in Km and a decrease in Vmax was observed. The Ki plot was linear and the curves intersect on the left of the 1/V versus [I] plot. These data characterize an inhibition of the mixed type. Although the 2,5-HD concentration that inhibited AChE activity is high compared to that attainable in occupationally exposed workers, these data are useful in understanding the neurotoxicity of this compound. Furthermore, the effect of 2,5-HD on AChE activity must not be a consequence of its effects as an organic solvent on protein structure, because total inhibition induced by 2,5-HD was partially reversed by increasing substrate concentration.
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