scholarly journals Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by scanning mutagenesis

2010 ◽  
Vol 136 (3) ◽  
pp. 339-352 ◽  
Author(s):  
Timothy J. Wilding ◽  
Kevin Chen ◽  
James E. Huettner
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Kainate Receptors ◽  
Transmembrane Helices ◽  
Ionic Selectivity ◽  
Chloride Permeability ◽  
Central Cavity ◽  
Whole Cell ◽  
Fatty Acid Inhibition

RNA editing of kainate receptor subunits at the Q/R site determines their susceptibility to inhibition by cis-unsaturated fatty acids as well as block by cytoplasmic polyamines. Channels comprised of unedited (Q) subunits are strongly blocked by polyamines, but insensitive to fatty acids, such as arachidonic acid (AA) and docosahexaenoic acid (DHA), whereas homomeric edited (R) channels resist polyamine block but are inhibited by AA and DHA. In the present study, we have analyzed fatty acid modulation of whole-cell currents mediated by homomeric recombinant GluK2 (formerly GluR6) channels with individual residues in the pore-loop, M1 and M3 transmembrane helices replaced by scanning mutagenesis. Our results define three abutting surfaces along the M1, M2, and M3 helices where gain-of-function substitutions render GluK2(Q) channels susceptible to fatty acid inhibition. In addition, we identify four locations in the M3 helix (F611, L614, S618, and T621) at the level of the central cavity where Arg substitution increases relative permeability to chloride and eliminates polyamine block. Remarkably, for two of these positions, L614R and S618R, exposure to fatty acids reduces the apparent chloride permeability and potentiates whole-cell currents ∼5 and 2.5-fold, respectively. Together, our results suggest that AA and DHA alter the orientation of M3 in the open state, depending on contacts at the interface between M1, M2, and M3. Moreover, our results demonstrate the importance of side chains within the central cavity in determining ionic selectivity and block by cytoplasmic polyamines despite the inverted orientation of GluK2 as compared with potassium channels and other pore-loop family members.

scholarly journals Amino Acid Substitutions in the Pore Helix of GluR6 Control Inhibition by Membrane Fatty Acids

2008 ◽  
Vol 132 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Timothy J. Wilding ◽  
Elisabeth Fulling ◽  
Yun Zhou ◽  
James E. Huettner
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Kainate Receptors ◽  
Kainate Receptor ◽  
Strong Inhibition ◽  
Wild Type ◽  
Hek 293 ◽  
Channel Inhibition ◽  
293 Cells ◽  
Fatty Acid Inhibition

RNA editing at the Q/R site in the GluR5 and GluR6 subunits of neuronal kainate receptors regulates channel inhibition by lipid-derived modulators including the cis-unsaturated fatty acids arachidonic acid and docosahexaenoic acid. Kainate receptor channels in which all of the subunits are in the edited (R) form exhibit strong inhibition by these compounds, whereas wild-type receptors that include a glutamine (Q) at the Q/R site in one or more subunits are resistant to inhibition. In the present study, we have performed an arginine scan of residues in the pore loop of the GluR6(Q) subunit. Amino acids within the range from −19 to +7 of the Q/R site of GluR6(Q) were individually mutated to arginine and the mutant cDNAs were expressed as homomeric channels in HEK 293 cells. All but one of the single arginine substitution mutants yielded functional channels. Only weak inhibition, typical of wild-type GluR6(Q) channels, was observed for substitutions +1 to +6 downstream of the Q/R site. However, arginine substitution at several locations upstream of the Q/R site resulted in homomeric channels exhibiting strong inhibition by fatty acids, which is characteristic of homomeric GluR6(R) channels. Based on homology with the pore loop of potassium channels, locations at which R substitution induces susceptibility to fatty acid inhibition face away from the cytoplasm toward the M1 and M3 helices and surrounding lipids.

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.

A POSSIBLE MECHANISM FOR FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1957 ◽  
Vol 35 (1) ◽  
pp. 645-653
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Liver Homogenate ◽  
Acid Inhibition ◽  
Acetyl Coa ◽  
Fatty Acid Inhibition

Further investigations have been carried out on the fatty acid inhibition of cholesterol biosynthesis in rat liver homogenates. A correlation appears to exist between cholesterol inhibition and the elongation of the carbon chain of saturated fatty acids containing an even number of carbon atoms. Neither saturated nor unsaturated fatty acids interfere with the formation of acetyl CoA by liver homogenate. The stage where acetoacetate is formed from acetyl CoA is suggested as a possible site for inhibition of cholesterol synthesis by fatty acids.

A POSSIBLE MECHANISM FOR FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1957 ◽  
Vol 35 (8) ◽  
pp. 645-653
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Liver Homogenate ◽  
Acid Inhibition ◽  
Acetyl Coa ◽  
Fatty Acid Inhibition

Further investigations have been carried out on the fatty acid inhibition of cholesterol biosynthesis in rat liver homogenates. A correlation appears to exist between cholesterol inhibition and the elongation of the carbon chain of saturated fatty acids containing an even number of carbon atoms. Neither saturated nor unsaturated fatty acids interfere with the formation of acetyl CoA by liver homogenate. The stage where acetoacetate is formed from acetyl CoA is suggested as a possible site for inhibition of cholesterol synthesis by fatty acids.

EFFECT OF GINGER, LEMURU FISH OIL SAPONIFICATION AND OLIVE OIL ON COMPOSITION FATTY ACID OF BEEF

2014 ◽  
Vol 4 (1) ◽  
pp. 31-39
Author(s):  
Siwitri Kadarsih
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Olive Oil ◽  
Rice Bran ◽  
Dry Matter ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Omega 3 ◽  
Omega 6

The objective was to get beef that contain unsaturated fatty acids (especially omega 3 and 6), so as to improve intelligence, physical health for those who consume. The study design using CRD with 3 treatments, each treatment used 4 Bali cattle aged approximately 1.5 years. Observations were made 8 weeks. Pasta mixed with ginger provided konsentrat. P1 (control); P2 (6% saponification lemuru fish oil, olive oil 1%; rice bran: 37.30%; corn: 62.70%; KLK: 7%, ginger paste: 100 g); P3 (lemuru fish oil saponification 8%, 2% olive oil; rice bran; 37.30; corn: 62.70%; KLK: 7%, ginger paste: 200 g). Konsentrat given in the morning as much as 1% of the weight of the cattle based on dry matter, while the grass given a minimum of 10% of the weight of livestock observation variables include: fatty acid composition of meat. Data the analyzies qualitative. The results of the study showed that the composition of saturated fatty acids in meat decreased and an increase in unsaturated fatty acids, namely linoleic acid (omega 6) and linolenic acid (omega 3), and deikosapenta deikosaheksa acid.Keywords : 

scholarly journals Explore the gene network regulating the composition of fatty acids in cottonseed

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lihong Ma ◽  
Xinqi Cheng ◽  
Chuan Wang ◽  
Xinyu Zhang ◽  
Fei Xue ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Linolenic Acid ◽  
Gene Network ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Accumulation Pattern ◽  
Time Points ◽  
Expression Characteristics

Abstract Background Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. Results In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5–15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10–60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25–50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. Conclusions These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

scholarly journals A non-canonical Δ9-desaturase synthesizing palmitoleic acid identified in the thraustochytrid Aurantiochytrium sp. T66

2021 ◽  
Author(s):  
E-Ming Rau ◽  
Inga Marie Aasen ◽  
Helga Ertesvåg
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Palmitoleic Acid ◽  
Unsaturated Fatty Acids ◽  
Gene Annotation ◽  
Vaccenic Acid ◽  
Strain Engineering ◽  
Δ9 Desaturase ◽  
Δ12 Desaturase

Abstract Thraustochytrids are oleaginous marine eukaryotic microbes currently used to produce the essential omega-3 fatty acid docosahexaenoic acid (DHA, C22:6 n-3). To improve the production of this essential fatty acid by strain engineering, it is important to deeply understand how thraustochytrids synthesize fatty acids. While DHA is synthesized by a dedicated enzyme complex, other fatty acids are probably synthesized by the fatty acid synthase, followed by desaturases and elongases. Which unsaturated fatty acids are produced differs between different thraustochytrid genera and species; for example, Aurantiochytrium sp. T66, but not Aurantiochytrium limacinum SR21, synthesizes palmitoleic acid (C16:1 n-7) and vaccenic acid (C18:1 n-7). How strain T66 can produce these fatty acids has not been known, because BLAST analyses suggest that strain T66 does not encode any Δ9-desaturase-like enzyme. However, it does encode one Δ12-desaturase-like enzyme. In this study, the latter enzyme was expressed in A. limacinum SR21, and both C16:1 n-7 and C18:1 n-7 could be detected in the transgenic cells. Our results show that this desaturase, annotated T66Des9, is a Δ9-desaturase accepting C16:0 as a substrate. Phylogenetic studies indicate that the corresponding gene probably has evolved from a Δ12-desaturase-encoding gene. This possibility has not been reported earlier and is important to consider when one tries to deduce the potential a given organism has for producing unsaturated fatty acids based on its genome sequence alone. Key points • In thraustochytrids, automatic gene annotation does not always explain the fatty acids produced. • T66Des9 is shown to synthesize palmitoleic acid (C16:1 n-7). • T66des9 has probably evolved from Δ12-desaturase-encoding genes.

scholarly journals Meat Quality, Fatty Acid Content and NMR Metabolic Profile of Dorper Sheep Supplemented with Bypass Fats

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1133
Author(s):  
Atique Ahmed Behan ◽  
Muhammad Tayyab Akhtar ◽  
Teck Chwen Loh ◽  
Sharida Fakurazi ◽  
Ubedullah Kaka ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Meat Quality ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Fatty Acid Content ◽  
Basal Diet ◽  
Negative Influence ◽  
Significant Difference ◽  
Dorper Sheep

The supplementation of rumen bypass fat (RBF) has remained one of the preferred approaches used to decrease undesirable saturated fatty acids (FA) and increase beneficial unsaturated FA in the meat. This study was planned to evaluate the influences of rumen bypass fats on meat quality, fatty acid and metabolic profiles in male Dorper sheep (n = 36) with 24.66 ± 0.76 kg (mean ± standard error) initial body weight. Treatment comprised a basal diet (30:70 rice straw to concentrate) with no added RBF as a control (CON), basal diet with prilled fat (PF), basal diet with prilled fat plus lecithin (PFL) and basal diet with calcium soap of palm fatty acids (CaS). The findings revealed that cooking loss, drip loss and shear force in longissimus dorsi (LD) muscle were not affected by RBF supplementation, while meat pH was significantly higher in the CaS on aging day 1. However, the diet supplemented with prilled fat and lecithin modified the meat’s fatty acid profile significantly by increasing unsaturated fatty acids and decreasing saturated fats. The relative quantification of the major differentiating metabolites found in LD muscle of sheep showed that total cholesterol, esterified cholesterol, choline, glycerophosphocholine and glycerophospholipids were significantly lower in CaS and PFL diets, while glycerol and sphingomyelin were significantly higher in CaS and PFL diets. Most of the metabolites in the liver did not show any significant difference. Based on our results, the supplementation of protected fats did not have a negative influence on meat quality and the meat from Dorper sheep fed prilled fat with lecithin contained more healthy fatty acids compared to other diets.

Modifying egg fatty acid content by supplementation of laying hen diets with palm olein oil (POO)

2009 ◽  
Vol 2009 ◽  
pp. 212-212
Author(s):  
S J Hosseini Vashan ◽  
N Afzali ◽  
A Golian ◽  
M Malekaneh ◽  
A Allahressani
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Acid Content ◽  
Palm Olein ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Fatty Acid Content ◽  
Processing Plant ◽  
Optimum Level ◽  
Olein Oil

Palm oil is the most abundant of all oils produced globally. It is very high in saturated fatty acids specifically palmitic acid, but other fatty acids (monounsaturated (MUFA) and polyunsaturated) are presented at low concentrations. In the processing plant some high amount of oleic acid with some other unsaturated fatty acids are extracted and marketed as Palm olein oil, and used to reduce blood or egg cholesterol (Rievelles et al., 1994). The objective of this study was to determine the optimum level of dietary palm olein oil required to enrich the mono-unsaturated fatty acid content of yolk, egg cholesterol and antibody titre.

Sign in / Sign up

Export Citation Format

Share Document