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

被引：0
作者：
Mehmet Berk Akay
Kübra Şener
Suat Sari
Ebru Bodur
机构：
[1] Hacettepe University,Faculty of Medicine, Department of Medical Biochemistry
[2] Gazi University,Faculty of Science, Department of Biology
[3] Hacettepe University,Faculty of Pharmacy, Department of Pharmaceutical Chemistry
来源：
The Protein Journal | 2023年 / 42卷
关键词：
Acetylcholinesterase; arachidonic acid; linoleic acid; linolenic acid; inhibition kinetics; molecular docking;
D O I：
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学科分类号：
摘要：
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 IC50 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 IC50 value of 2.78 µM and Ki value of 396.35 µM. Linoleic acid, an essential 18-carbon fatty acid (18:2 n-6, cis 9,12) had an IC50 value of 7.95 µM and Ki value of 8027.55 µM. The IC50 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.
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页码：96 / 103
页数：7
相关论文
共 97 条
[1]  
Cokugraş AN(2003)Butyrylcholinesterase: structure and physiological importance Turk J Biochem 28 54-61
[2]  
Massoulie J(1993)Molecular and cellular biology of cholinesterases Prog Neurobiol 41 31-91
[3]  
Pezzementi L(2015)Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses Pharmacol Ther 148 34-46
[4]  
Bon S(1997)Differences in active site gorge dimensions of cholinesterases revealed by binding of inhibitors to human butyrylcholinesterase Biochemistry 36 14642-14651
[5]  
Krejci E(2004)Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer’s disease Eur J Pharmacol 486 9-17
[6]  
Vallette FM(1992)Effect of dietary fats on erythrocyte membrane lipid composition and membrane-bound enzyme activities Metabolism 41 352-358
[7]  
Lockridge O(2016)Butyrylcholinesterase expression is regulated by fatty acids in HepG2 cells Chem Biol Interact 259 276-281
[8]  
Saxena A(2016)The discovery and early structural studies of arachidonic acid J Lipid Res 57 1126-1132
[9]  
Redman AM(2006)Polyunsaturated fatty acids: biotechnology Crit Rev Biotechnol 26 83-93
[10]  
Jiang X(2018)Cytochrome P450 in the central nervous system as a therapeutic target in neurodegenerative diseases Drug Metab Rev 50 95-108
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