The effects of zinc on the multi-catalytic activities of acetylcholinesterase and butyrylcholinesterase

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Wilson, Daniel Bernard

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University of Guelph

Abstract

The modulatory effects of zinc on the catalytic activities of Acetylcholinesterase (AChE, E.C. 3.1.1.7) and Butyrylcholinesterase (BChE, E.C. 3.1.1.8) were studied in vitro, ex vivo, and in vivo. In vitro, the dose-response effects of zinc, manganese, and magnesium on the activities of eel AChE and horse serum BChE were assessed. Ex vivo, divalent cation dose-response studies were conducted on the activities of rat plasma and cerebral cortex extracts. In the in vitro studies, no specific effects of zinc were observed. However, divalent cation activation of EeAChE acetylcholinesterase, and BChE butyrylcholinesterase and arylacylamidase activities were observed. Ex vivo, zinc specifically inhibited cerebral cortex acetylcholinesterase and butyrylcholinesterase activities, suggesting zinc may be an allosteric-like inhibitor of cortical AChE. In vivo, the reversal of dietary zinc deficiency by physiological and pharmacological levels of zinc was studied in male weanling rats. Plasma acetylcholinesterase and butyrylcholinesterase, and cerebral cortex arylacylamidase activities were reduced by zinc deficiency and normalized with repletion. The response of the plasma cholinesterases resembled that of a zinc metalloenzyme. A dietary control study demonstrated that the reduction in plasma cholinesterase activities observed in zinc deficient rats was not due to reduced food intake. Instantantaneous and time-dependent inhibition studies with various chelating agents were subsequently conducted on the activities of various cholinesterase enzymes (eel AChE, recombinant human AChE, horse serum BChE, and rat plasma cholinesterases). Plasma BChE was found to be substantially inhibited by 1,10-phenanthroline, but only mildly by the non-chelating analog, 4,7-phenanthroline, further suggesting that it may be a zinc metalloenzyme. In conclusion, zinc is a physiological modulator of Butyrylcholinesterase.

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modulatory effects, zinc, catalytic activities, Acetylcholinesterase, Butyrylcholinesterase, in vitro, ex vivo, in vivo

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