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Journal of Lipid Research Jan 2019Exosomes are a type of extracellular vesicle released from cells after fusion of multivesicular bodies with the plasma membrane. These vesicles are often enriched in... (Review)
Review
Exosomes are a type of extracellular vesicle released from cells after fusion of multivesicular bodies with the plasma membrane. These vesicles are often enriched in cholesterol, SM, glycosphingolipids, and phosphatidylserine. Lipids not only have a structural role in exosomal membranes but also are essential players in exosome formation and release to the extracellular environment. Our knowledge about the importance of lipids in exosome biology is increasing due to recent technological developments in lipidomics and a stronger focus on the biological functions of these molecules. Here, we review the available information about the lipid composition of exosomes. Special attention is given to ether lipids, a relatively unexplored type of lipids involved in membrane trafficking and abundant in some exosomes. Moreover, we discuss how the lipid composition of exosome preparations may provide useful information about their purity. Finally, we discuss the role of phosphoinositides, membrane phospholipids that help to regulate membrane dynamics, in exosome release and how this process may be linked to secretory autophagy. Knowledge about exosome lipid composition is important to understand the biology of these vesicles and to investigate possible medical applications.
Topics: Animals; Ether; Exosomes; Humans; Phosphatidylinositols
PubMed: 30076207
DOI: 10.1194/jlr.R084343 -
Cell Death and Differentiation Aug 2021It is well established that ferroptosis is primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation by free...
It is well established that ferroptosis is primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation by free radicals or enzymatic stimulation of lipoxygenase. Although there is emerging evidence that long-chain saturated fatty acid (SFA) might be implicated in ferroptosis, it remains unclear whether and how SFA participates in the process of ferroptosis. Using endogenous metabolites and genome-wide CRISPR screening, we have identified FAR1 as a critical factor for SFA-mediated ferroptosis. FAR1 catalyzes the reduction of C16 or C18 saturated fatty acid to fatty alcohol, which is required for the synthesis of alkyl-ether lipids and plasmalogens. Inactivation of FAR1 diminishes SFA-dependent ferroptosis. Furthermore, FAR1-mediated ferroptosis is dependent on peroxisome-driven ether phospholipid biosynthesis. Strikingly, TMEM189, a newly identified gene which introduces vinyl-ether double bond into alkyl-ether lipids to generate plasmalogens abrogates FAR1-alkyl-ether lipids axis induced ferroptosis. Our study reveals a new FAR1-ether lipids-TMEM189 axis dependent ferroptosis pathway and suggests TMEM189 as a promising druggable target for anticancer therapy.
Topics: Ether; Ferroptosis; Humans; Peroxisomes; Phospholipids
PubMed: 33731874
DOI: 10.1038/s41418-021-00769-0 -
Molecules (Basel, Switzerland) Dec 2022The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study,...
The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study, the semisynthesis of 28 furofuran lignans using samin () as the starting material is described. Our methodology involved the protonation of samin () to generate an oxocarbenium ion followed by the attack from two different nucleophiles, namely, thiols (RSH) and alcohols (ROH). The highly diastereoselective thioether and ether furofuran lignans were obtained, and their configurations were confirmed by 2D NMR and X-ray crystallography. The mechanism underlying the reaction was studied by monitoring H NMR and computational calculations, that is, the diastereomeric α- and β-products were equally formed through the S1-like mechanism, while the β-product was gradually transformed via an S2-like mechanism to the α-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against α-glucosidases and free radicals, the lignans and of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the α-glucosidase inhibition of and were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both and possessed promising antidiabetic activity, while simultaneously inhibiting α-glucosidases and free radicals.
Topics: Lignans; alpha-Glucosidases; Ether; Free Radicals; Ethyl Ethers; Ethers; Molecular Structure
PubMed: 36558136
DOI: 10.3390/molecules27249001 -
Anaesthesia Oct 2016
Topics: Anesthetics, Inhalation; Drug Misuse; Ether; Humans; Hydrocarbons, Fluorinated; Nitrous Oxide
PubMed: 27393489
DOI: 10.1111/anae.13551 -
Protein & Cell Feb 2018Ether lipids, such as plasmalogens, are peroxisome-derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached... (Review)
Review
Ether lipids, such as plasmalogens, are peroxisome-derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond, as opposed to an ester bond in the more common diacyl phospholipids. This seemingly simple biochemical change has profound structural and functional implications. Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes. Ether lipids are also important for the organization and stability of lipid raft microdomains, cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants, and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Here, we review the biology of ether lipids and their potential significance in human disorders, including neurological diseases, cancer, and metabolic disorders.
Topics: Animals; Disease; Ether; Humans; Lipid Metabolism; Lipids
PubMed: 28523433
DOI: 10.1007/s13238-017-0423-5 -
Anaesthesia Oct 1963
Topics: Air; Anesthesia; Anesthesia, Inhalation; Ether; Ethers; Humans; Trichloroethylene
PubMed: 14071375
DOI: 10.1111/j.1365-2044.1963.tb13571.x -
Nature Communications Apr 2022Darobactin is a ribosomally synthesized and post-translationally modified peptide (RiPP), which possesses potent activity against various Gram-negative bacteria....
Darobactin is a ribosomally synthesized and post-translationally modified peptide (RiPP), which possesses potent activity against various Gram-negative bacteria. Darobactin features a highly unique bicyclic scaffold, consisting of an ether crosslink between two Trp residues and a C-C crosslink between a Lys and a Trp. Here we report in vivo and in vitro activity of darobactin synthase DarE. We show DarE is a radical S-adenosylmethionine (rSAM) enzyme and is solely responsible for forming the bicyclic scaffold of darobactin. DarE mainly produced the ether-crosslinked product in vitro, and when the assay was performed in HO, apparent O incorporation was observed into the ether-crosslinked product. These observations suggested an rSAM-dependent process in darobactin biosynthesis, involving a highly unusual oxygen insertion step from a water molecule and subsequent O-H and C-H activations. Genome mining analysis demonstrates the diversity of darobactin-like biosynthetic gene clusters, a subclade of which likely encode monocyclic products with only an ether linkage. We propose the name daropeptide for this growing family of ether-containing RiPPs produced by DarE enzymes.
Topics: Ether; Ethers; Peptides; Phenylpropionates; S-Adenosylmethionine
PubMed: 35487921
DOI: 10.1038/s41467-022-30084-2 -
Organic & Biomolecular Chemistry Nov 2022A new class of push-pull-activated alkynes featuring di- and trifluorinated ynol ethers was synthesized. The difluorinated ynol ether exhibited an optimal balance of...
A new class of push-pull-activated alkynes featuring di- and trifluorinated ynol ethers was synthesized. The difluorinated ynol ether exhibited an optimal balance of stability and reactivity, displaying a substantially improved half-life in the presence of aqueous thiols over the previously reported 1-haloalkyne analogs while reacting just as fast in the hydroamination reaction with ,-diethylhydroxylamine. The trifluorinated ynol ether reacted significantly faster, exhibiting a second order rate constant of 0.56 M s in methanol, but it proved too unstable toward thiols. These fluorinated ynol ethers further demonstrate the importance of the hyperconjugation-rehybridization effect in activating alkynes and demonstrate how substituent effects can both activate and stabilize alkynes for bioorthogonal reactivity.
Topics: Ethers; Ether; Alkynes; Sulfhydryl Compounds
PubMed: 36367436
DOI: 10.1039/d2ob01917e -
Microbiology Spectrum Oct 2022Coabalamin-dependent -demethylase in sp. strain MRG-PMF1 was found to catalyze the unprecedented allyl aryl ether cleavage reaction. To expand the potential...
Coabalamin-dependent -demethylase in sp. strain MRG-PMF1 was found to catalyze the unprecedented allyl aryl ether cleavage reaction. To expand the potential biotechnological applications, the reaction mechanism of the allyl aryl ether C-O bond cleavage, proposed to utilize the reactive Co(I) supernucleophile species, was studied further from the anaerobic whole-cell biotransformation. Various allyl naphthyl ether derivatives were reacted with sp. MRG-PMF1 -demethylase, and stereoisomers of allyl naphthyl ethers, including prenyl and but-2-enyl naphthyl ethers, were converted to the corresponding naphthol in a stereoselective manner. The allyl aryl ether cleavage reaction was regioselective, and 2-naphthyl ethers were converted faster than the corresponding 1-naphthyl ethers. However, MRG-PMF1 cocorrinoid -demethylase was not able to convert (2-methylallyl) naphthyl ether substrates, and the conversion of propargyl naphthyl ether was extremely slow. From the results, it was proposed that the allyl ether cleavage reaction follows the nucleophilic conjugate substitution (S2') mechanism. The reactivity and mechanism of the new allyl ether cleavage reaction by cobalamin-dependent -demethylase would facilitate the application of sp. MRG-PMF1 -demethylase in the area of green biotechnology. Biodegradation of environmental pollutants and valorization of biomaterials in a greener way is of great interest. Cobalamin-dependent -demethylase in sp. MRG-PMF1 exclusively involves anaerobic C1 metabolism by cleaving the C-O bond of aromatic methoxy group and also produces various aryl alcohols by metabolizing allyl aryl ether compounds. Whereas methyl ether cleavage reaction is known to follow the S2' mechanism, the reaction pattern and mechanism of the new allyl ether cleavage reaction by cobalamin-dependent -demethylase have never been studied. For the first time, stereoselectivity and the S2' mechanism of allyl aryl ether cleavage reaction by sp. MRG-PMF1 -demethylase is reported, and the results would facilitate the application of sp. MRG-PMF1 -demethylase in the area of green biotechnology.
Topics: Ether; Oxidoreductases, O-Demethylating; Naphthols; Ethers; Ethyl Ethers; Vitamin B 12; Methyl Ethers; Environmental Pollutants; Biocompatible Materials
PubMed: 36197289
DOI: 10.1128/spectrum.03305-22 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Ether; Humans; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental
PubMed: 10476394
DOI: No ID Found