Novel activity of human BChE: Lipid hydrolysis

Biochimie. 2023 Jan:204:127-135. doi: 10.1016/j.biochi.2022.09.008. Epub 2022 Sep 17.


Acetylcholinesterase and butyrylcholinesterase (BChE) typically hydrolyze the neurotransmitter acetylcholine. The multifunctional enzyme BChE is associated with lipid metabolism through an undefined mechanism. Based on lipid-related studies and by comparing the structural similarities between lipases and BChE we postulated that the association of BChE with lipid metabolism could occur through hydrolytic activity. Utilizing purified BChE enzymes from different sources and several lipases as controls, the ability of BChE to hydrolyze 4-methylumbelliferyl (4-mu) palmitate is investigated. Using lectin affinity, inhibition kinetics, and molecular modeling, we demonstrated that purified BChE hydrolyzed 4-mu palmitate at pH 8 as effectively as wheat germ lipase. The affinity Km value of the enzymes for 4-mu palmitate as substrate is found as 10.4 μM, 34.2 μM, 129.8 μM, and 186 μM for wheat germ lipase, purified BChE, pancreatic lipase, and commercial BChE, respectively. Analysis of the inhibitory effect of 4-mu palmitate on BChE using butyrylthiocholine as substrate revealed competitive inhibition with Ki and IC50 values of 448 μM and 987.2 μM, respectively. The binding affinity and interactions of 4-mu palmitate with BChE and pancreatic lipase were predicted by molecular docking. These results suggest that BChE possesses lipolytic activity. The possibility that BChE hydrolyzes not only 4-mu palmitate but also other types of lipids will lead to a new approach to those disease states associated with increased BChE activity/expression.

Keywords: 4-mu palmitate; Butyrylcholinesterase; Enzyme kinetics; Lipid hydrolysis; Molecular docking; Multifunctionality.

MeSH terms

  • Acetylcholinesterase* / metabolism
  • Butyrylcholinesterase*
  • Cholinesterase Inhibitors / pharmacology
  • Humans
  • Hydrolysis
  • Lipase
  • Lipids
  • Molecular Docking Simulation


  • Butyrylcholinesterase
  • Acetylcholinesterase
  • Lipase
  • Lipids
  • Cholinesterase Inhibitors