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International Journal of Molecular... Oct 2021The selenoprotein family includes 25 members, many of which are antioxidant or redox regulating enzymes. A unique member of this family is Selenoprotein I (SELENOI),... (Review)
Review
The selenoprotein family includes 25 members, many of which are antioxidant or redox regulating enzymes. A unique member of this family is Selenoprotein I (SELENOI), which does not catalyze redox reactions, but instead is an ethanolamine phosphotransferase (Ept). In fact, the characteristic selenocysteine residue that defines selenoproteins lies far outside of the catalytic domain of SELENOI. Furthermore, data using recombinant SELENOI lacking the selenocysteine residue have suggested that the selenocysteine amino acid is not directly involved in the Ept reaction. SELENOI is involved in two different pathways for the synthesis of phosphatidylethanolamine (PE) and plasmenyl PE, which are constituents of cellular membranes. Ethanolamine phospholipid synthesis has emerged as an important process for metabolic reprogramming that occurs in pluripotent stem cells and proliferating tumor cells, and this review discusses roles for upregulation of SELENOI during T cell activation, proliferation, and differentiation. SELENOI deficiency lowers but does not completely diminish de novo synthesis of PE and plasmenyl PE during T cell activation. Interestingly, metabolic reprogramming in activated SELENOI deficient T cells is impaired and this reduces proliferative capacity while favoring tolerogenic to pathogenic phenotypes that arise from differentiation. The implications of these findings are discussed related to vaccine responses, autoimmunity, and cell-based therapeutic approaches.
Topics: Cellular Reprogramming; Ethanolamine; Ethanolaminephosphotransferase; Humans; Lymphocyte Activation; Phosphatidylethanolamines; Phospholipids; Selenium; Selenocysteine; Selenoproteins; T-Lymphocytes; Up-Regulation
PubMed: 34681834
DOI: 10.3390/ijms222011174 -
Journal of the American Chemical Society Nov 2019A molecular signal displayed on the external surface of one population of vesicles was used to trigger a catalytic process on the inside of a second population of...
A molecular signal displayed on the external surface of one population of vesicles was used to trigger a catalytic process on the inside of a second population of vesicles. The key recognition event is the transfer of a protein (NeutrAvidin) bound to vesicles displaying desthiobiotin to vesicles displaying biotin. The desthiobiotin-protein complex was used to anchor a synthetic transducer in the outer leaflet of the vesicles, and when the protein was displaced, the transducer translocated across the bilayer to expose a catalytic headgroup to the internal vesicle solution. As a result, an ester substrate encapsulated on the inside of this second population of vesicles was hydrolyzed to give a fluorescence output signal. The protein has four binding sites, which leads to multivalent interactions with membrane-anchored ligands and very high binding affinities. Thus, biotin, which has a dissociation constant 3 orders of magnitude higher than desthiobiotin, did not displace the protein from the membrane-anchored transducer, and membrane-anchored biotin displayed on the surface of a second population of vesicles was required to generate an effective input signal.
Topics: Artificial Cells; Avidin; Biotin; Lipid Bilayers; Liposomes; Phosphatidylcholines; Phosphatidylethanolamines; Signal Transduction
PubMed: 31642667
DOI: 10.1021/jacs.9b09102 -
Bioconjugate Chemistry Sep 2020Liposomes have proven to be effective nanocarriers due to their ability to encapsulate and deliver a wide variety of therapeutic cargo. A key goal of liposome research...
Liposomes have proven to be effective nanocarriers due to their ability to encapsulate and deliver a wide variety of therapeutic cargo. A key goal of liposome research is to enhance control over content release at diseased sites. Though a number of stimuli have been explored for triggering liposomal release, reactive oxygen species (ROS), which have received significantly less attention, provide excellent targets due to their key roles in biology and overabundance in diseased cells. Here, we report a ROS-responsive liposome platform through the inclusion of lipid bearing a boronate ester headgroup and a quinone-methide (QM) generating self-immolative linker attached onto a dioleoylphosphatidylethanolamine (DOPE) lipid scaffold. Fluorescence-based dye release assays validated that this system enables release of both hydrophobic and hydrophilic contents upon hydrogen peroxide (HO) addition. Details of the release process were carefully studied, and data showed that oxidative removal of the boronate headgroup is sufficient to result in hydrophobic content release, while production of DOPE is needed for hydrophilic cargo leakage. These results showcase that lipid can serve as a promising ROS-responsive liposomal delivery platform for controlled release.
Topics: Boron Compounds; Delayed-Action Preparations; Fluorescent Dyes; Indolequinones; Liposomes; Phosphatidylethanolamines; Reactive Oxygen Species
PubMed: 32808755
DOI: 10.1021/acs.bioconjchem.0c00397 -
Nature Structural & Molecular Biology Jun 2024Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the...
Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the sphingomyelin synthase (SMS) family, comprising SMS1, SMS2 and SMS-related (SMSr) members. Although SMS1 and SMS2 exhibit SMS activity, SMSr possesses ceramide phosphoethanolamine synthase activity. Here we determined the cryo-electron microscopic structures of human SMSr in complexes with ceramide, diacylglycerol/phosphoethanolamine and ceramide/phosphoethanolamine (CPE). The structures revealed a hexameric arrangement with a reaction chamber located between the transmembrane helices. Within this structure, a catalytic pentad E-H/D-H-D was identified, situated at the interface between the lipophilic and hydrophilic segments of the reaction chamber. Additionally, the study unveiled the two-step synthesis process catalyzed by SMSr, involving PE-PLC (phosphatidylethanolamine-phospholipase C) hydrolysis and the subsequent transfer of the phosphoethanolamine moiety to ceramide. This research provides insights into the catalytic mechanism of SMSr and expands our understanding of sphingolipid metabolism.
Topics: Humans; Transferases (Other Substituted Phosphate Groups); Cryoelectron Microscopy; Sphingomyelins; Models, Molecular; Ceramides; Ethanolamines; Phosphatidylethanolamines; Diglycerides; Nerve Tissue Proteins; Membrane Proteins
PubMed: 38388831
DOI: 10.1038/s41594-024-01237-2 -
Food Chemistry Dec 2019The contents of N-acylphosphatidylethanolamines (NAPEs), N-acylethanolamines (NAEs) and endocannabinoids (ECs) in 43 food products were assessed and daily intakes, based...
The contents of N-acylphosphatidylethanolamines (NAPEs), N-acylethanolamines (NAEs) and endocannabinoids (ECs) in 43 food products were assessed and daily intakes, based on consumption of Mediterranean, vegetarian and Western diets, were simulated. NAPEs and NAEs were more abundant in plant-based foods than in animal food products; NAPEs were in the ranges 0-4032 vs 4-398 µg/g dw and NAEs were in the ranges 0-35 vs 0.1-0.7 µg/g dw, respectively while ECs were in the range 0-0.1 vs 0-34 µg/g dw. Daily intakes of NAPEs and NAEs were higher from Mediterranean (263 and 0.25 mg/day) and vegetarian (242 and 0.28 mg/day) diets than the Western diet (163 and 0.08 mg/day). Conversely, ECs intakes were higher from Western and Mediterranean diets (0.17 mg/day) than the vegetarian diet (0.01 mg/day). Future studies will evaluate the physiological role of dietary NAPEs, NAEs and ECs in humans.
Topics: Animals; Databases, Factual; Diet; Diet, Mediterranean; Diet, Vegetarian; Diet, Western; Endocannabinoids; Ethanolamines; Food Analysis; Phosphatidylethanolamines
PubMed: 31351254
DOI: 10.1016/j.foodchem.2019.125218 -
Journal of Microbiology and... Jul 2022A white-pigmented, non-motile, gram-negative, and rod-shaped bacterium, designated CYS-02, was isolated from soil sampled at Suwon, Gyeonggi-do, Republic of Korea. Cells...
A white-pigmented, non-motile, gram-negative, and rod-shaped bacterium, designated CYS-02, was isolated from soil sampled at Suwon, Gyeonggi-do, Republic of Korea. Cells were strictly aerobic, grew optimally at 20-28ºC and hydrolyzed Tween 40. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain CYS-02 formed a lineage within the family and clustered as members of the genus . The closest members were DSM 27352 (98.6% sequence similarity), NBRC 15149 (98.5%), and JM-310 (98.3%). The principal respiratory quinone was Q-8 and the major polar lipids contain phosphatidylethanolamine (PE), phosphatidylethanolamine (PG), and diphosphatidylglycerol (DPG). The predominant cellular fatty acids were C, summed feature 3 (C7c and/or C6c) and summed feature 8 (C7c and/or C6c). The DNA GC content was 67.7 mol%. The ANI and dDDH values between strain CYS-02 and the closest members in the genus were ≤ 79.0 and 22.4%, respectively, and the AAI and POCP values between CYS-02 and the other related species in the family were > 70% and > 50%, respectively. The genome of strain CYS-02 showed a putative terpene biosynthetic cluster responsible for antioxidant activity which was supported by DPPH radical scavenging activity test. Based on genomic, phenotypic and chemotaxonomic analyses, strain CYS-02 was classified into a novel species in the genus , for which the name sp. nov., has been proposed. The type strain is CYS-02 (= KACC 22656 = NBRC 115645 [corrected] ).
Topics: Antioxidants; Bacterial Typing Techniques; Comamonadaceae; DNA, Bacterial; Fatty Acids; Phosphatidylethanolamines; Phospholipids; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Soil; Soil Microbiology
PubMed: 35791077
DOI: 10.4014/jmb.2205.05018 -
Molecules (Basel, Switzerland) Nov 2020Polymer dispersed liquid crystals (PDLCs) have kindled a spark of interest because of their unique characteristic of electrically controlled switching. However, some... (Review)
Review
Polymer dispersed liquid crystals (PDLCs) have kindled a spark of interest because of their unique characteristic of electrically controlled switching. However, some issues including high operating voltage, low contrast ratio and poor mechanical properties are hindering their practical applications. To overcome these drawbacks, some measures were taken such as molecular structure optimization of the monomers and liquid crystals, modification of PDLC and doping of nanoparticles and dyes. This review aims at detailing the recent advances in the process, preparations and applications of PDLCs over the past six years.
Topics: Carbon; Coloring Agents; Liquid Crystals; Membranes, Artificial; Nanostructures; Optics and Photonics; Phosphatidylethanolamines; Polymerization; Polymers; Structure-Activity Relationship
PubMed: 33255525
DOI: 10.3390/molecules25235510 -
Nature Communications May 2024The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and...
The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and immune/neurological disorders. Here, we apply native mass spectrometry (MS)-based approaches to provide evidence of super-dimer formation (LAT1-4F2hc). When combined with lipidomics, and site-directed mutagenesis, we discover four endogenous phosphatidylethanolamine (PE) molecules at the interface and C-terminus of both LAT1 subunits. We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP), we reveal that super-dimerization is sensitive to pH, and modulated by complex N-glycans on the 4F2hc subunit. We further validate the dynamic assemblies of LAT1-4F2hc on plasma membrane and in the lysosome. Together our results link PTM and lipid binding with regulation and localisation of the LAT1-4F2hc super-dimer.
Topics: Humans; Large Neutral Amino Acid-Transporter 1; Phosphatidylethanolamines; Lipoylation; Lysosomes; Cell Membrane; Amino Acid Transport System y+; HEK293 Cells; Protein Multimerization; Protein Binding; Mass Spectrometry; Mutagenesis, Site-Directed; Hydrogen-Ion Concentration; Membrane Proteins; Fusion Regulatory Protein 1, Heavy Chain; Adaptor Proteins, Signal Transducing
PubMed: 38697966
DOI: 10.1038/s41467-024-47948-4 -
Comprehensive Identification of Amadori Compound-Modified Phosphatidylethanolamines in Human Plasma.Chemical Research in Toxicology Jul 2019Amadori compound modified lipids are the result of nonenzymatic glycation and play an important role in several physiological and pathological processes. However,...
Amadori compound modified lipids are the result of nonenzymatic glycation and play an important role in several physiological and pathological processes. However, glycation of phosphatidylethanolamine (PE), the most abundant amine-containing lipid in blood plasma, is underexplored and so far only a few glycated PEs have been reported. Herein, we report comprehensive profiling of Amadori-PE and -LysoPE species in human plasma. Using synthetic standards, we first optimized the enrichment procedure for extracting Amadori-PE/LysoPE from plasma. On the basis of the characteristic neutral losses of 303 Da in positive and 162 Da in negative ionization mode, we then applied neural loss scanning-liquid chromatography tandem mass spectrometry (LC-NLS-MS) to identify potentially glycated PE and LysoPE, which was followed by targeted product ion scanning (LC-PIS-MS) to confidently confirm the fatty acyl substitutions of the modified lipids. A total of 20 Amadori-LysoPE and 62 Amadori-PE species, including diacyl, plasmanyl, and plasmenyl, were identified. Among them, the concentrations of 12 Amarodi-LysoPE and 54 Amadori-PE were also quantified in native human plasma, using stable isotope labeled Amadori lipids as internal standards.
Topics: Chromatography, Liquid; Glycosylation; Humans; Molecular Structure; Phosphatidylethanolamines; Tandem Mass Spectrometry
PubMed: 31188577
DOI: 10.1021/acs.chemrestox.9b00158 -
International Journal of Molecular... Jan 2023Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the...
Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation.
Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of disease progression and evaluating the effects of specific phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS/MS). HepG2 (hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in NAFLD/NASH development. Several PLs and their relative ratios were significantly associated with NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis, lipid oxidation, autophagy, apoptosis, inflammation, and fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the disease progression of obesity associated NAFLD, likely through a causal cascade of impacts on the function of different liver cells.
Topics: Humans; Adult; Non-alcoholic Fatty Liver Disease; Liver; Phosphatidylethanolamines; Hepatic Stellate Cells; Tandem Mass Spectrometry; Obesity; Disease Progression
PubMed: 36674549
DOI: 10.3390/ijms24021034