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Xenobiotica
the fate of foreign compounds in biological systems
Volume 49, 2019 - Issue 7
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General Xenobiochemistry

Computational and experimental studies on the interaction between butyrylcholinesterase and fluoxetine: implications in health and disease

, , , & ORCID Icon
Pages 803-810 | Received 23 May 2018, Accepted 26 Jul 2018, Published online: 29 Nov 2018
 

Abstract

  1. Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.

  2. Here, our aim was to study the interaction between BChE and fluoxetine.

  3. Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59 ± 0.36 U mg−1 protein, 194 ± 14 µM, 1.3 × 108 s−1 and 6.7 × 105 µM−1s−1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104 µM and a Ki value of 36.3 ± 4.7 µM.

  4. Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.

Disclosure statement

No potential conflict of interest was reported by the authors.

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