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Inhibitory Action of Omega-3 and Omega-6 Fatty Acids Alpha-Linolenic, Arachidonic and Linoleic acid on Human Erythrocyte Acetylcholinesterase.

Mehmet Berk AkayKübra ŞenerSuat SariEbru Bodur
Published in: The protein journal (2022)
Acetylcholinesterase (AChE, E.C. 3.1.1.7) termed as the true cholinesterase functions to end cholinergic transmission at synapses. Due to its diverse expression in non-neural tissues such as erythrocytes and bones along with its various molecular forms, researchers seek a non-classical role for this protein. Here, the inhibitory action of unsaturated 18 carbon fatty acids linoleic acid and alpha-linolenic acid and 20 carbon fatty acid arachidonic acid on AChE were investigated. Enzyme activity was measured in kinetic assay method according to Ellman assay utilizing acetylthiocholine. Analysis of the activity data revealed that among the fatty acids examined the IC 50 values differed according to the length of the fatty acid and the number of the double bonds. Arachidonic acid, a 20-carbon fatty acid with 4 unsaturated bonds (20:4 n-6, cis 5,8,11,14) displayed an IC 50 value of 2.78 µM and K i value of 396.35 µM. Linoleic acid, an essential 18-carbon fatty acid (18:2 n-6, cis 9,12) had an IC 50 value of 7.95 µM and K i value of 8027.55 µM. The IC 50 value of alpha-linolenic acid, 18-carbon fatty acid (18:3 n-3, cis-9,12,15) was found as 179.11 µM. Analysis of the data fit the inhibition mechanism for linoleic, alpha-linolenic and arachidonic acid as mixed-type; non-competitive. Molecular docking complied with these results yielding the best score for arachidonic acid. The alkenyl chain of the fatty acids predictably reached to the catalytic site while the carboxylate strongly interacted with the peripheric anionic site.
Keyphrases
  • fatty acid
  • molecular docking
  • poor prognosis
  • high throughput
  • endothelial cells
  • gene expression
  • machine learning
  • small molecule
  • molecular dynamics simulations
  • single molecule
  • big data