scholarly journals Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Noah M Dietzen ◽  
Mark J Arcario ◽  
Lawrence J Chen ◽  
John T Petroff ◽  
Trent K Moreland ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Palmitic Acid ◽  
Binding Sites ◽  
Transmembrane Domain ◽  
Bound State ◽  
Inhibitory Effect ◽  
Coarse Grained ◽  
Fatty Acid Binding

Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than palmitic acid, similar to the effects observed in the GABAA receptor and nicotinic acetylcholine receptor. Using photo-affinity labeling and coarse-grained molecular dynamics simulations, we identified two fatty acid binding sites in the outer transmembrane domain (TMD) of ELIC. Fatty acid binding to the photolabeled sites is selective for DHA over palmitic acid, and specific for an agonist-bound state. Hexadecyl-methanethiosulfonate modification of one of the two fatty acid binding sites in the outer TMD recapitulates the inhibitory effect of PUFAs in ELIC. The results demonstrate that DHA selectively binds to multiple sites in the outer TMD of ELIC, but that state-dependent binding to a single intrasubunit site mediates DHA inhibition of ELIC.

scholarly journals Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites

2021 ◽  
Author(s):  
Noah M Dietzen ◽  
Mark J Arcario ◽  
Lawrence J Chen ◽  
John T Petroff ◽  
Kathiresan Krishnan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Palmitic Acid ◽  
Binding Sites ◽  
Transmembrane Domain ◽  
Bound State ◽  
Inhibitory Effect ◽  
Coarse Grained ◽  
Fatty Acid Binding

Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than palmitic acid, similar to the effects observed in the GABA(A) receptor and nicotinic acetylcholine receptor. Using photo-affinity labeling and coarse-grained molecular dynamics simulations, we identified two fatty acid binding sites in the outer transmembrane domain (TMD) of ELIC. Fatty acid binding to the photolabeled sites is selective for DHA over palmitic acid, and specific for an agonist-bound state. Hexadecyl-methanethiosulfonate modification of one of the two fatty acid binding sites in the outer TMD recapitulates the inhibitory effect of PUFAs in ELIC. The results demonstrate that DHA selectively binds to multiple sites in the outer TMD of ELIC, but that state-dependent binding to a single intrasubunit site mediates DHA inhibition of ELIC.

Fatty acid binding sites of rodent adipocyte and heart fatty acid binding proteins: characterization using fluorescent fatty acids

Biochemistry ◽  
1990 ◽  
Vol 29 (40) ◽  
pp. 9305-9311 ◽  
Author(s):  
Margo G. Wootan ◽  
Nathan M. Bass ◽  
David A. Bernlohr ◽  
Judith Storch
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Sites ◽  
Binding Proteins ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding

scholarly journals 14-P005 The role of fatty acid binding proteins and polyunsaturated fatty acids in hippocampal neurogenesis

2009 ◽  
Vol 126 ◽  
pp. S240
Author(s):  
Noriko Osumi ◽  
Miho Matsumata ◽  
Nobuyuki Sakayori ◽  
Motoko Maekawa ◽  
Takeo Yoshikawa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Binding Proteins ◽  
Hippocampal Neurogenesis ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding

scholarly journals Allosterically Coupled Multisite Binding of Testosterone to Human Serum Albumin

Endocrinology ◽  
2020 ◽  
Vol 162 (2) ◽  
Author(s):  
Abhilash Jayaraj ◽  
Heidi A Schwanz ◽  
Daniel J Spencer ◽  
Shalender Bhasin ◽  
James A Hamilton ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Human Serum Albumin ◽  
Fluorescence Spectroscopy ◽  
Serum Albumin ◽  
Binding Sites ◽  
Equilibrium Dialysis ◽  
2D Nmr ◽  
Fatty Acid Binding ◽  
Binding Isotherms

Abstract Human serum albumin (HSA) acts as a carrier for testosterone, other sex hormones, fatty acids, and drugs. However, the dynamics of testosterone’s binding to HSA and the structure of its binding sites remain incompletely understood. Here, we characterize the dynamics of testosterone’s binding to HSA and the stoichiometry and structural location of the binding sites using 2-dimensional nuclear magnetic resonance (2D NMR), fluorescence spectroscopy, 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid dipotassium salt partitioning, and equilibrium dialysis, complemented by molecular modeling. 2D NMR studies showed that testosterone competitively displaced 18-[13C]-oleic acid from at least 3 known fatty acid binding sites on HSA that also bind many drugs. Binding isotherms of testosterone’s binding to HSA generated using fluorescence spectroscopy and equilibrium dialysis were nonlinear and the apparent dissociation constant varied with different concentrations of testosterone and HSA. The binding isotherms neither conformed to a linear binding model with 1:1 stoichiometry nor to 2 independent binding sites; the binding isotherms were most consistent with 2 or more allosterically coupled binding sites. Molecular dynamics studies revealed that testosterone’s binding to fatty acid binding site 3 on HSA was associated with conformational changes at site 6, indicating that residues in in these 2 distinct binding sites are allosterically coupled. There are multiple, allosterically coupled binding sites for testosterone on HSA. Testosterone shares these binding sites on HSA with free fatty acids, which could displace testosterone from HSA under various physiological states or disease conditions, affecting its bioavailability.

scholarly journals Determination of Seasonal Changes on Lipid Content and Fatty Acids of Nemipterus randalli (Russell, 1986) from Mersin Bay

2020 ◽  
Vol 8 (8) ◽  
pp. 1623-1629
Author(s):  
Mısra Bakan ◽  
Nahit Soner Börekçi ◽  
Deniz Ayas
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Lipid Content ◽  
Seasonal Changes ◽  
Monounsaturated Fatty Acids ◽  
Spring Season

In this study, the seasonal changes on lipid content and fatty acid levels of Nemipterus randalli from the Mersin Bay have been determined. Total lipid levels were found as 3.17%, 2.12%, 0.63%, and 0.72% in spring, summer, autumn and winter seasons, respectively. The fatty acid composition of this species is composed of 30 fatty acids. Major fatty acids are palmitic acid (C16:0) and stearic acid (C18:0) from saturated fatty acids (SFAs) oleic acid (C18:1n9c) and 11-docosenoic acid (ceteloic; C22:1n11) from monounsaturated fatty acids (MUFAs) and eicosapentaenoic acid (EPA; C20: 5n3), and docosahexaenoic acid (DHA; C22: 6n3) from polyunsaturated fatty acids (PUFAs). The highest level of palmitic acid was detected in the winter season, and the palmitic acid level varied between 15.41% and 20.72% (77.79-433.30 mg/100g). The highest level of stearic acid was determined in the spring season, and its levels varied between 14.75% and 19.14%, and its levels were also determined as 77.95-483.91 mg/100g. Oleic acid from the monounsaturated fatty acids varied between 5.46% and 7.98%, and its levels were found to be 31.98-224.38 mg/100g. Ceteloic acid varied between 5.73% and 7.80%, and its levels were determined to be 33.01-161.11 mg/100g. The EPA levels from the polyunsaturated fatty acids ranged from 4.34 to 5.34%, and its levels were found to be 19.30-137.50 mg/100g. The highest levels of DHA were detected in autumn, its levels varied between 21.09% and 23.00%, and its levels have also been detected as 102.30-604.25 mg/100g. The highest levels of Σn3, Σn6 and Σn9 were found in the spring season. The levels of Σn3, Σn6 and Σn9 varied between 26.73-27.19% (122.89-751.59 mg/100g), 4.19-4.79% (18.63-134.68 mg/100g) and 5.95-9.79% (35.22-247.15 mg/100g), respectively. AI and TI values in N. randalli were found at 0.28-0.36% and 0.33-0.36%, respectively.

scholarly journals Effect of feeding linseed on the fatty acid composition of milk

2013 ◽  
pp. 45-50
Author(s):  
Ágnes Süli ◽  
Béla Béri ◽  
János Csapó ◽  
Éva Vargáné Visi
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Palmitic Acid ◽  
Linolenic Acid ◽  
Myristic Acid ◽  
Saturated Fatty Acids

In the last decades many researches were made to change the animal product food’s composition. The production of better fat-compound milk and dairy products became a goal in the name of health conscious nutrition. These researches were motivated by the non adequate milk fat’s fatty acid composition. There have been made researches in order to modify the milk’s fatty acids’ composition to reach the expectations of functional foods. With the optimal supplement of the feed can be increased the proportion of the polyunsaturated fatty acids and can decreased the saturated fatty acids. Row fat content of milk was not decreasing in the course of examination neither of the cold extruded linseed nor the whole linseed supplement as opposed to observations experienced by other authors. In case of monounsaturated and polyunsaturated fatty acids when supplementing with cold extruded linseed the most significant change was observable in the concentration of the elaidic acid, oleic acid, linoleic acid, alfa-linolenic acid, conjugated linoleic acid. In case of saturated fatty acids the quantity of palmitic acid and myristic acid lowered considerably. When observating the feeding with whole linseed the concentration of many fatty acids from the milkfat of saturated fatty acids lowered (caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid). The quantity of some unsaturated fatty acids was showing a distinct rise after feeding with linseed, this way the oleic acid, alfa-linolenic acid, conjugated linoleic acid, eicosadienoic acid. The aim of the study was to produce food which meets the changed demands of customers as well. The producing of milk with favourable fatty acid content from human health point of view can give scope propagate the products of animal origin.  

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