-
Biochimica Et Biophysica Acta Oct 2016This review summarises high resolution studies on the interface of lamellar lipid bilayers composed of the most typical lipid molecules which constitute the lipid matrix... (Review)
Review
This review summarises high resolution studies on the interface of lamellar lipid bilayers composed of the most typical lipid molecules which constitute the lipid matrix of biomembranes. The presented results were obtained predominantly by computer modelling methods. Whenever possible, the results were compared with experimental results obtained for similar systems. The first and main section of the review is concerned with the bilayer-water interface and is divided into four subsections. The first describes the simplest case, where the interface consists only of lipid head groups and water molecules and focuses on interactions between the lipid heads and water molecules; the second describes the interface containing also mono- and divalent ions and concentrates on lipid-ion interactions; the third describes direct inter-lipid interactions. These three subsections are followed by a discussion on the network of direct and indirect inter-lipid interactions at the bilayer interface. The second section summarises recent computer simulation studies on the interactions of antibacterial membrane active compounds with various models of the bacterial outer membrane. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
Topics: Computer Simulation; Hydrogen Bonding; Lipid Bilayers; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylserines; Sphingomyelins; Water
PubMed: 26825705
DOI: 10.1016/j.bbamem.2016.01.024 -
Molecules (Basel, Switzerland) Dec 2019Reactive oxygen species (ROS) and their derivatives, reactive aldehydes (RAs), have been implicated in the pathogenesis of many diseases, including metabolic,... (Review)
Review
Reactive oxygen species (ROS) and their derivatives, reactive aldehydes (RAs), have been implicated in the pathogenesis of many diseases, including metabolic, cardiovascular, and inflammatory disease. Understanding how RAs can modify the function of membrane proteins is critical for the design of therapeutic approaches in the above-mentioned pathologies. Over the last few decades, direct interactions of RA with proteins have been extensively studied. Yet, few studies have been performed on the modifications of membrane lipids arising from the interaction of RAs with the lipid amino group that leads to the formation of adducts. It is even less well understood how various multiple adducts affect the properties of the lipid membrane and those of embedded membrane proteins. In this short review, we discuss a crucial role of phosphatidylethanolamine (PE) and PE-derived adducts as mediators of RA effects on membrane proteins. We propose potential PE-mediated mechanisms that explain the modulation of membrane properties and the functions of membrane transporters, channels, receptors, and enzymes. We aim to highlight this new area of research and to encourage a more nuanced investigation of the complex nature of the new lipid-mediated mechanism in the modification of membrane protein function under oxidative stress.
Topics: Animals; Humans; Lipid Peroxidation; Membrane Proteins; Oxidative Stress; Phosphatidylethanolamines; Reactive Oxygen Species
PubMed: 31842328
DOI: 10.3390/molecules24244545 -
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 -
The Journal of Biological Chemistry Jul 2014Recently, synthetic prions with a high level of specific infectivity have been produced from chemically defined components in vitro. A major insight arising from these... (Review)
Review
Recently, synthetic prions with a high level of specific infectivity have been produced from chemically defined components in vitro. A major insight arising from these studies is that various classes of host-encoded cofactor molecules such as phosphatidylethanolamine and RNA molecules are required to form and maintain the specific conformation of infectious prions. Synthetic mouse prions formed with phosphatidylethanolamine exhibit levels of specific infectivity ∼1 million-fold greater than "protein-only" prions (Deleault, N. R., Walsh, D. J., Piro, J. R., Wang, F., Wang, X., Ma, J., Rees, J. R., and Supattapone, S. (2012) Proc. Natl. Acad. Sci. U.S.A. 109, E1938-E1946). Moreover, cofactor molecules also appear to regulate prion strain properties by limiting the potential conformations of the prion protein (see Deleault et al. above). The production of fully infectious synthetic prions provides new opportunities to study the mechanism of prion infectivity directly by structural and biochemical methods.
Topics: Animals; Cricetinae; Mice; Phosphatidylethanolamines; PrPSc Proteins; Prion Diseases; Prions; Protein Conformation
PubMed: 24860097
DOI: 10.1074/jbc.R113.511329 -
Journal of Lipid Research Aug 2010An amino group of phosphatidylethanolamine (PE) is considered as a target for nonenzymatic glycation, and the potential involvement of lipid glycation in the...
An amino group of phosphatidylethanolamine (PE) is considered as a target for nonenzymatic glycation, and the potential involvement of lipid glycation in the pathogenesis of diabetic complications has generated interest. However, unlike an early glycation product of PE (Amadori-PE), the occurrence and roles of advanced glycation end products of PE (AGE-PE) in vivo have been unclear. Here, we developed an LC-MS/MS method for the analysis of AGE-PE [carboxymethyl-PE (CM-PE) and carboxyethyl-PE (CE-PE)]. Collision-induced dissociation of CM-PE and CE-PE produced characteristic ions, permitting neutral loss scanning (NLS) and multiple reaction monitoring (MRM) of AGE-PE. By NLS analysis, a series of AGE-PE molecular species was detected in human erythrocytes and blood plasma. In LC-MS/MS analysis, MRM enabled the separation and determination of the predominant AGE-PE species. Between healthy subjects and diabetic patients, no significant differences were observed in AGE-PE concentrations in erythrocytes and plasma, whereas Amadori-PE concentrations were higher in diabetic patients. These results provide direct evidence for the presence of AGE-PE in human blood, and indicated that, compared with Amadori-PE, AGE-PE is less likely to be accumulated in diabetic blood. The presently developed LC-MS/MS method appears to be a powerful tool for understanding in vivo lipid glycation and its pathophysiological consequence.
Topics: Blood Chemical Analysis; Case-Control Studies; Chromatography, Liquid; Diabetes Mellitus; Erythrocytes; Female; Glycation End Products, Advanced; Humans; Hyperglycemia; Male; Middle Aged; Phosphatidylethanolamines; Tandem Mass Spectrometry; Young Adult
PubMed: 20386060
DOI: 10.1194/jlr.D004564 -
Biochimica Et Biophysica Acta.... Sep 2020NMR is a sophisticated method for investigation of structure and dynamics of lipid and protein molecules in membranes. Vibrational spectroscopy is also powerful because... (Review)
Review
NMR is a sophisticated method for investigation of structure and dynamics of lipid and protein molecules in membranes. Vibrational spectroscopy is also powerful because of relatively high resolution and sensitivity, and easier access than NMR. A combined use of these spectroscopies could provide important insights into the membrane biophysics. A structural analysis of phosphatidylethanolamine (PE) bilayers in built-up films by infrared dichroism suggested that polar groups oriented parallel to the membrane surface. A Raman analysis of phosphatidylcholine (PC) revealed that the gauche conformation was preferred for the choline backbone not only in solid, but also in the gel and liquid-crystalline states. The polar group structure of DPPC bilayers in the liquid-crystalline state was determined by analyzing deuterium quadrupole splitting of the choline group and phosphorus chemical shift anisotropy of the phosphate group in combination with restriction of the gauche conformation of the choline group determined by Raman spectroscopy. This was an excellent complementarity of NMR and vibrational spectroscopies. The deuterium quadrupole splitting values mentioned above were found to change on addition of ions such as NaCl, CaCl, and LaCl, suggesting that a structural change takes place on ion binding and the polar group of PC works as an electric charge sensor of membranes. The ion-bound structure was determined by NMR using the restriction from Raman spectroscopy. The PN vector of phosphorylcholine group was inclined by 63° from the membrane surface, while the inclination was 18° in the ion-free form. The deuterium quadrupole splitting values and phosphorus powder patterns revealed that on mixing with phosphatidylglycerol (PG) or cardiolipin (CL), PC did not change its dynamic structure of the glycerol backbone, but PE did. The mixture of PE with PG or CL shared a new dynamic structure, suggesting their adaptive miscibility in the molecular level. PC was molecularly immiscible with any of PE, PG, and CL. The molecular miscibility would regulate not only interactions of proteins with mixed bilayers but also formation of asymmetric lipid membranes. Interactions of crown-ether (CE) modified artificial microbial peptides with phospholipid bilayers were investigated by NMR and FTIR. CE-modified 14-mers with one or two basic amino acid residues revealed position-specific selectivity for the suppression of calcein leakage from PC vesicles but did not for that from PG vesicles, suggesting that structures of the lipid polar groups play crucial roles in different responses of the vesicles to the positively charged peptides. Manipulation of the peptide-polar group interaction can be used for drug design.
Topics: Cardiolipins; Lipid Bilayers; Nuclear Magnetic Resonance, Biomolecular; Phosphatidylethanolamines; Phosphatidylglycerols; Spectrum Analysis, Raman
PubMed: 32407775
DOI: 10.1016/j.bbamem.2020.183352 -
Bioscience Reports Feb 2021Cell membranes have important functions in many steps of the blood coagulation cascade, including the activation of factor X (FX) by the factor VIIa (FVIIa)-tissue...
Cell membranes have important functions in many steps of the blood coagulation cascade, including the activation of factor X (FX) by the factor VIIa (FVIIa)-tissue factor (TF) complex (extrinsic Xase). FVIIa shares structural similarity with factor IXa (FIXa) and FXa. FIXa and FXa are regulated by binding to phosphatidylserine (PS)-containing membranes via their γ-carboxyglutamic acid-rich domain (Gla) and epidermal growth-factor (EGF) domains. Although FVIIa also has a Gla-rich region, its affinity for PS-containing membranes is much lower compared with that of FIXa and FXa. Research suggests that a more common endothelial cell lipid, phosphatidylethanolamine (PE), might augment the contribution of PS in FVIIa membrane-binding and proteolytic activity. We used soluble forms of PS and PE (1,2-dicaproyl-sn-glycero-3-phospho-l-serine (C6PS), 1,2-dicaproyl-sn-glycero-3-phospho-ethanolamine (C6PE)) to test the hypothesis that the two lipids bind to FVIIa jointly to promote FVIIa membrane binding and proteolytic activity. By equilibrium dialysis and tryptophan fluorescence, we found two sites on FVIIa that bound equally to C6PE and C6PS with Kd of ∼ 150-160 μM, however, deletion of Gla domain reduced the binding affinity. Binding of lipids occurred with greater affinity (Kd∼70-80 μM) when monitored by FVIIa proteolytic activity. Global fitting of all datasets indicated independent binding of two molecules of each lipid. The proteolytic activity of FVIIa increased by ∼50-100-fold in the presence of soluble TF (sTF) plus C6PS/C6PE. However, the proteolytic activity of Gla-deleted FVIIa in the presence of sTF was reduced drastically, suggesting the importance of Gla domain to maintain full proteolytic activity.
Topics: Fluorescence; Humans; Phosphatidylethanolamines; Phosphatidylserines; Proteolysis; Prothrombin; Structure-Activity Relationship; Thromboplastin; Tryptophan
PubMed: 33479740
DOI: 10.1042/BSR20204077 -
Cell Death and Differentiation Mar 2015Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates....
Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE) positively regulates autophagy. Reduction of intracellular PE levels by knocking out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated chronological ageing-associated production of reactive oxygen species and death. Conversely, the artificial increase of intracellular PE levels, by provision of its precursor ethanolamine or by overexpression of the PE-generating enzyme Psd1, significantly increased autophagic flux, both in yeast and in mammalian cell culture. Importantly administration of ethanolamine was sufficient to extend the lifespan of yeast (Saccharomyces cerevisiae), mammalian cells (U2OS, H4) and flies (Drosophila melanogaster). We thus postulate that the availability of PE may constitute a bottleneck for functional autophagy and that organismal life or healthspan could be positively influenced by the consumption of ethanolamine-rich food.
Topics: Animals; Autophagy; Cell Line, Tumor; Drosophila melanogaster; Humans; Longevity; Phosphatidylethanolamines; Yeasts
PubMed: 25571976
DOI: 10.1038/cdd.2014.219 -
Journal of Lipid Research Jul 2008Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is interrelated. Both phospholipids are components of mammalian... (Review)
Review
Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is interrelated. Both phospholipids are components of mammalian cell membranes and play important roles in biological processes such as apoptosis and cell signaling. PS is synthesized in mammalian cells by base-exchange reactions in which polar head groups of preexisting phospholipids are replaced by serine. PS synthase activity resides primarily on mitochondria-associated membranes and is encoded by two distinct genes. Studies in mice in which each gene has been individually disrupted are beginning to elucidate the importance of these two synthases for biological functions in intact animals. PE is made in mammalian cells by two completely independent major pathways. In one pathway, PS is converted into PE by the mitochondrial enzyme PS decarboxylase. In addition, PE is made via the CDP-ethanolamine pathway, in which the final reaction occurs on the endoplasmic reticulum and nuclear envelope. The relative importance of these two pathways of PE synthesis has been investigated in knockout mice. Elimination of either pathway is embryonically lethal, despite the normal activity of the other pathway. PE can also be generated from a base-exchange reaction and by the acylation of lyso-PE. Cellular levels of PS and PE are tightly regulated by the implementation of multiple compensatory mechanisms.
Topics: Animals; Apoptosis; CDPdiacylglycerol-Serine O-Phosphatidyltransferase; Cytidine Diphosphate; Humans; Phosphatidylethanolamines; Phosphatidylserines
PubMed: 18204094
DOI: 10.1194/jlr.R700020-JLR200 -
Blood Sep 2012Phospholipids are of critical importance in mammalian cell biology, both through providing a permeability barrier and acting as substrates for synthesis of lipid... (Review)
Review
Phospholipids are of critical importance in mammalian cell biology, both through providing a permeability barrier and acting as substrates for synthesis of lipid mediators. Recently, several new families of bioactive lipids were identified that form through the enzymatic oxidation of membrane phospholipids in circulating innate immune cells and platelets. These comprise eicosanoids attached to phosphatidylethanolamine and phosphatidylcholine and form within 2-5 minutes of cell activation by pathophysiologic agonists, via the coordinated action of receptors and enzymes. In this review, we summarize what is currently known regarding their structures, mechanisms of formation, cell biology, and signaling actions. We show that phospholipid oxidation by acutely activated immune cells is a controlled event, and we propose a central role in regulating membrane biology and innate immune function during health and disease. We also review the mass spectrometry methods used for identification of the lipids and describe how these approaches can be used for discovery of new lipid mediators in complex biologic samples.
Topics: Animals; Blood Platelets; Cell Communication; Eicosanoids; Humans; Immunity, Innate; Macrophages; Mass Spectrometry; Mice; Monocytes; Oxidation-Reduction; Phosphatidylcholines; Phosphatidylethanolamines; Signal Transduction
PubMed: 22802337
DOI: 10.1182/blood-2012-04-402826