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. Here, our aim was to study the interaction between BChE and fluoxetine. 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. 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.
Keywords: Fluoxetine; butyrylcholinesterase; enzyme inhibition; molecular docking.