Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

International Journal of Molecular Sciences

Miroslav Pohanka¹ 

[1] Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 50001 Hradec Kralove, Czech Republic

关键词: acetylcholinesterase;    butyrylcholinesterase;    caffeine;    Alzheimer disease;    myasthenia gravis;    acetylcholine;    inhibition;    coffee;    alkaloid;    chocolate;   

DOI  :  10.3390/ijms14059873

来源: mdpi

【 摘 要 】

Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, K_i, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as K_i was found to be 175 ± 9 μmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland