scholarly journals Investigating the Inhibitory Effect of Fatty Acids on NMDA Receptor

2018 ◽  
Vol 2 (1) ◽  
pp. 18
Author(s):  
Tian yun Ma ◽  
Philip Chen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Nmda Receptor ◽  
Ampa Receptor ◽  
Memory Loss ◽  
Inhibitory Effect ◽  
Receptor Inhibition ◽  
Electrode Voltage ◽  
Inward Currents ◽  
Nmdar Subunit

<p><em>Previous research has showed that AMPA receptor can be used as a molecular target for anti-epileptic drugs, and there is evidence of an inhibitory effect of several fatty acids on AMPA receptor, for example, </em><em>D</em><em>ecanoic </em><em>A</em><em>cid (DA), 4-</em><em>E</em><em>thyl </em><em>O</em><em>ctanoic </em><em>A</em><em>cid (4EOA) and 4-</em><em>B</em><em>utyl</em><em>c</em><em>y</em><em> C</em><em>loheaxne </em><em>C</em><em>arboxylic </em><em>A</em><em>cid (4BCCA). However, as NMDA receptor and AMPA receptor are quite similar in structures and are widely distributed in CNS, there is a concern on whether the three fatty acids also have an effect on NMDA receptor, and NMDA receptor inhibition may result in some unwanted side effects, such as hallucinations, nightmares, and memory loss. Two-electrode voltage clamp was performed on the oocytes of Xenopus Laevis expressing the NMDAR subunit GluN1/N2A, to record agonist evoked inward currents generated from oocytes exposed to different concentrations of fatty acid solutions. On further examination it was found that all of the three acids have some inhibitory effect on NMDA recceptor, and seem to act as non-competitive antagonists. The 4EOA has the strongest inhibition effect on NMDA receptor, followed by 4BCCA and DA. However, the three fatty acids only have a clear inhibitory effect when the concentration of the corresponding fatty acid is higher than 500 µM, which is considered high for clinical use. Moreover, the fatty acids tested had a stronger inhibitory effect on NMDA receptor containing the GluN1/N2B subunits.</em></p>

scholarly journals Evidence for the regulation of guinea-pig heart microsomal phosphatidylcholine-hydrolysing phospholipase A1 by guanosine 5′-[γ-thio]triphosphate

1992 ◽  
Vol 288 (3) ◽  
pp. 965-968 ◽  
Author(s):  
K Badiani ◽  
X Lu ◽  
G Arthur
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Guinea Pig ◽  
Molecular Species ◽  
Inhibitory Effect ◽  
Phospholipase A1 ◽  
Guinea Pig Heart ◽  
Substrate Specificities ◽  
Rate Of Hydrolysis ◽  
Hydrolysis Of

We have recently characterized lysophospholipase A2 activities in guinea-pig heart microsomes and postulated that these enzymes act sequentially with phospholipases A1 to release fatty acids selectively from phosphatidylcholine (PC) and phosphatidylethanolamine, thus providing an alternative route to the phospholipase A2 mode of release. In a further investigation of the postulated pathway, we have characterized the PC-hydrolysing phospholipase A1 in guinea-pig heart microsomes. Our results show that the enzyme may have a preference for substrates with C16:0 over C18:0 at the sn-1 position. In addition, although the enzyme cleaves the sn-1 fatty acid, the rate of hydrolysis of PC substrates with C16:0 at the sn-1 position was influenced by the nature of the fatty acid at the sn-2 position. The order of decreasing preference was C18:2 > C20:4 = C18:1 > C16:0. The hydrolyses of the molecular species were differentially affected by heating at 60 degrees C. An investigation into the effect of nucleotides on the activity of the enzyme showed that guanosine 5′-[gamma-thio]triphosphate (GTP[S]) inhibited the hydrolysis of PC by phospholipase A1 activity, whereas GTP, guanosine 5′-[beta-thio]diphosphate (GDP[S]), GDP, ATP and adenosine 5′-[gamma-thio]triphosphate (ATP[S]) did not affect the activity. The inhibitory effect of GTP[S] on phospholipase A1 activity was blocked by preincubation with GDP[S]. A differential effect of GTP[S] on the hydrolysis of different molecular species was also observed. Taken together, the results of this study suggest the presence of more than one phospholipase A1 in the microsomes with different substrate specificities, which act sequentially with lysophospholipase A2 to release linoleic or arachidonic acid selectively from PC under resting conditions. Upon stimulation and activation of the G-protein, the release of fatty acids would be inhibited.

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.

Polyphenols and fatty acids responsible for anti-cyanobacterial allelopathic effects of submerged macrophyte Myriophyllum spicatum

2012 ◽  
Vol 66 (5) ◽  
pp. 993-999 ◽  
Author(s):  
S. Nakai ◽  
G. Zou ◽  
T. Okuda ◽  
W. Nishijima ◽  
M. Hosomi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Culture System ◽  
Myriophyllum Spicatum ◽  
Inhibitory Effect ◽  
Fatty Acid Mixture ◽  
Acid Mixture ◽  
Allelopathic Effect ◽  
Release Rates ◽  
Allelopathic Effects

Myriophyllum spicatum is known to inhibit the growth of cyanobacteria such as Microcystis aeruginosa by releasing anti-cyanobacterial allelochemicals. The allelochemicals possibly responsible for the inhibition include five polyphenols and three fatty acids, but the extent to which these are indeed responsible for the anti-cyanobacterial effects is unclear. The goal of this research was to determine the contribution of these compounds to the allelopathic effect of M. spicatum on M. aeruginosa. We first collected information on the release rates of these compounds and then added the compounds to a cyanobacterial medium on the basis of their release rates so as to simulate their excretion by M. spicatum. Addition of the polyphenols and fatty acids inhibited the growth of M. aeruginosa, and the interaction of the polyphenols and fatty acids was additive. The EC50 of a polyphenol and fatty acid mixture was compared with that of M. spicatum itself as previously determined in a mixed culture system in which M. spicatum and M. aeruginosa were incubated. The former was about 1.9 times higher than that of the latter, the implication being that the inhibitory effect of the polyphenols and fatty acids contributed about 53% of the allelopathic effect of M. spicatum. This paper is the first to describe allelochemicals that account for a half of the anti-cyanobacterial allelopathic effect of a macrophyte.

Effects of cholesterol on viability and (n – 6) fatty acid metabolism in cultured human monocyte-like cells (U937)

1992 ◽  
Vol 70 (8) ◽  
pp. 643-649 ◽  
Author(s):  
Andrew Howie ◽  
Yung-Sheng Huang ◽  
David F. Horrobin
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Human Monocyte ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
U937 Cells ◽  
Fetal Bovine ◽  
Cholesterol Supplementation

Effects of supplementation of growth-promoting cholesterol on metabolism of the cytotoxic (n – 6) polyunsaturated fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 0 or 38.7 μM cholesterol. The rate of uptake and the distribution of metabolites of (n – 6) fatty acids (such as 18:2(n – 6), 18:3(n – 6), and20:3(n – 6), and20:4(n – 6)) were examined by adding radiolabelled fatty acid at a level of 1 μg/mL (3.3 μM for 20-carbon fatty acids and 3.6 μM for 18-carbon fatty acids). For assessing the cytotoxicity, (n – 6) fatty acids were added to medium at a concentration of 5 μg/mL (16.4 μM for 20-carbon fatty acids and 17.9 μM for 18-carbon fatty acids). Cholesterol supplementation suppressed the uptake of all (n – 6) fatty acids and reduced the cytotoxic effects of 18:2(n – 6), 20:3(n – 6), and 20:4(n – 6), but not 18:3(n – 6). In addition, cholesterol supplementation increased peroxide production and metabolism of (n – 6) fatty acids in U937 cells. Thus, the differential suppressive effect of cholesterol on the cytotoxicity of different fatty acids could not be attributed to an inhibitory effect on fatty acid Δ6- and Δ5-desaturation, or to an antioxidant effect on peroxide formation.Key words: (n – 6) fatty acid metabolism, cytotoxicity, peroxides.

scholarly journals Utilization of methylmalonate for the synthesis of branched-chain fatty acids by preparations of chicken liver and sheep adipose tissue

1978 ◽  
Vol 176 (3) ◽  
pp. 799-804 ◽  
Author(s):  
J R Scaife ◽  
K W J Wahle ◽  
G A Garton
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Complex Mixture ◽  
Acid Synthesis ◽  
Inhibitory Effect ◽  
Chicken Liver ◽  
Malonyl Coa ◽  
Branched Chain

1. The utilization of methyl[2-14C]malonyl-CoA for fatty acid synthesis was investigated using synthetase preparations from chicken liver and sheep adipose tissue. 2. The rate of fatty acid synthesis from acetyl-CoA and malonyl-CoA was greatly diminished in the presence of methylmalonyl-CoA. 3. In the absence of malonyl-CoA, methylmalonyl-CoA was utilized for fatty acid synthesis only very slowly by the synthetase from sheep adipose tissue and not at all by that from chicken liver. 4. Despite the inhibitory effect of methylmalonyl-CoA on fatty acid synthesis from malonyl-CoA, it was utilized by the synthetase preparations from both species to produce a complex mixture of methyl-branched fatty acids.

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.

scholarly journals Evidence for dissociation of gluconeogenesis stimulated by non-esterified fatty acids and changes in fructose 2,6-bisphosphate in cultured rat hepatocytes

1992 ◽  
Vol 288 (1) ◽  
pp. 145-148 ◽  
Author(s):  
J N Clore ◽  
J S Stillman ◽  
S T Helm ◽  
W G Blackard
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
Fed State ◽  
Palmitate Oxidation ◽  
Lower Glucose ◽  
The Media ◽  
Cultured Rat Hepatocytes

In order to examine the role of fructose 2,6-bisphosphate (Fru-2,6-P2) in non-esterified-fatty-acid-stimulated gluconeogenesis, Fru-2,6-P2 levels were measured in cultured rat hepatocytes under conditions mimicking the fasted state. After addition of either 1.5 mM-palmitate or 10 nM-glucagon, [U-14C]lactate incorporation into glucose increased 2-fold, but only glucagon suppressed Fru-2,6-P2. Prevention of palmitate oxidation with a carnitine palmitoyltransferase-I inhibitor (2-bromopalmitate) diminished glucose production and Fru-2,6-P2 levels. Addition of exogenous glucose to the media increased Fru-2,6-P2 in a dose-related manner, which was further augmented by addition of palmitate. When Fru-2,6-P2 levels were examined in cells cultured under conditions mimicking the fed state (significantly higher basal Fru-2,6-P2 levels and lower glucose production), palmitate oxidation was associated with a significant fall in Fru-2,6-P2. In conclusion, the present studies have demonstrated a dissociation between fatty-acid-stimulated gluconeogenesis and changes in Fru-2,6-P2 in cultured rat hepatocytes. Further experiments suggest that the accumulation of intracellular hexose 6-phosphate as a result of fatty-acid-stimulated gluconeogenesis masks a putative inhibitory effect of fatty acids on Fru-2,6-P2 concentrations.

Unsaturated fatty acids inhibit ADP- arachidonate-induced platelet aggregation without affecting thromboxane synthesis

1986 ◽  
Vol 64 (9) ◽  
pp. 906-913 ◽  
Author(s):  
Ella Dratewka-Kos ◽  
D. O. Tinker ◽  
Brigitte Kindl
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Fatty Acid Inhibition ◽  
Induced Aggregation ◽  
Protein Free Medium

The inhibitory effects of three cis-unsaturated C18 fatty acids (oleic, linoleic, and linolenic acids, sodium salts) on ADP- and sodium-arachidonate-induced aggregation of washed rabbit platelets were investigated. When the platelets were suspended in protein-free medium containing dextran, it was found that these fatty acids at very low concentrations (2–45 μM) were potent inhibitors of platelet responsiveness and the inhibitory effect occurred within seconds. The inhibition of ADP-induced aggregation was not affected by abolishing the activity of platelet cyclooxygenase using aspirin. Human serum albumin relieved the inhibition caused by fatty acids for both ADP- and arachidonate-induced aggregation. The inhibitory effect of fatty acids does not seem to be due to decreased thromboxane formation (except possibly in the case of linolenate), and the relief of fatty acid inhibition by albumin does not potentiate thromboxane B2 formation from exogenous arachidonate. It is suggested that the inhibitory effect of polyunsaturated fatty acids on platelet aggregation is specific and not related to a general surfactant effect, since inhibition occurs far below the critical micelle concentration of fatty acid soaps.

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