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Progress in Lipid Research Apr 2021Phospholipid biosynthesis is crucial for plant growth and development. It involves attachment of fatty acids to a phospho-diacylglycerol backbone and modification of the... (Review)
Review
Phospholipid biosynthesis is crucial for plant growth and development. It involves attachment of fatty acids to a phospho-diacylglycerol backbone and modification of the phospho-group into an amino alcohol. The biochemistry and molecular biology of the former has been well established, but a number of enzymes responsible for the latter have only recently been cloned and functionally characterized in Arabidopsis and some other model plant species. The metabolism involving the polar head groups of phospholipids established by past biochemical studies can now be validated by available gene knockout models. Moreover, gene knockout studies have revealed emerging functions of phospholipids in regulating plant growth and development. This review aims to revisit the old questions of polar headgroup biosynthesis of plant phosphatidylcholine and phosphatidylethanolamine by giving an overview of recent advances in the field and beyond.
Topics: Arabidopsis; Fatty Acids; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids
PubMed: 33503494
DOI: 10.1016/j.plipres.2021.101091 -
Chemistry and Physics of Lipids Jul 2021Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug... (Review)
Review
Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug delivery, diagnosis, and in many other academic areas. A novel class of this nanoparticle is the actively target liposome, which is constructed with the surface modified with appropriated molecules (or ligands) to actively bind a target molecule of certain cells, system, or tissue. There are many ways to functionalize these nanostructures, from non-covalent adsorption to covalent bond formation. In this review, we focus on the strategies of modifying liposomes by glycerophospholipid covalent chemical reaction. The approach used in this text summarizes the main reactions and strategies used in phospholipid modification that can be carried out by chemists and researchers from other areas. The knowledge of these methodologies is of great importance for planning new studies using this material and also for manipulating its properties.
Topics: Liposomes; Nanoparticles; Phosphatidylethanolamines; Phospholipids; Polyethylene Glycols; Surface Properties
PubMed: 33891960
DOI: 10.1016/j.chemphyslip.2021.105084 -
Methods in Molecular Biology (Clifton,... 2023In animal tissues, N-acyltransferase (NAT) catalyzes the first reaction in the biosynthetic pathway of bioactive N-acylethanolamines, in which an acyl chain is...
In animal tissues, N-acyltransferase (NAT) catalyzes the first reaction in the biosynthetic pathway of bioactive N-acylethanolamines, in which an acyl chain is transferred from the sn-1 position of the donor phospholipid, such as phosphatidylcholine, to the amino group of phosphatidylethanolamine, resulting in the formation of N-acylphosphatidylethanolamine. NAT has long been known to be stimulated by Ca and hence referred to as Ca-dependent NAT. Later, this enzyme was identified as cPLAε (also referred to as PLA2G4E). On the other hand, members of the phospholipase A/acyltransferase (PLAAT) family (also known as HRAS-like suppressor family) show Ca-independent NAT activity. In this chapter, we describe (1) partial purification of Ca-dependent NAT from rat brain, (2) purification of recombinant cPLAε and PLAAT-2, and (3) NAT assay using radiolabeled substrate.
Topics: Acyltransferases; Animals; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipases A; Phospholipids; Rats
PubMed: 36152189
DOI: 10.1007/978-1-0716-2728-0_17 -
FEBS Letters Apr 2018Mitochondrial structure and function are influenced by the unique phospholipid composition of its membranes. While mitochondria contain all the major classes of... (Review)
Review
Mitochondrial structure and function are influenced by the unique phospholipid composition of its membranes. While mitochondria contain all the major classes of phospholipids, recent studies have highlighted specific roles of the nonbilayer-forming phospholipids phosphatidylethanolamine (PE) and cardiolipin (CL) in the assembly and activity of mitochondrial respiratory chain (MRC) complexes. The nonbilayer phospholipids are cone-shaped molecules that introduce curvature stress in the bilayer membrane and have been shown to impact mitochondrial fusion and fission. In addition to their overlapping roles in these mitochondrial processes, each nonbilayer phospholipid also plays a unique role in mitochondrial function; for example, CL is specifically required for MRC supercomplex formation. Recent discoveries of mitochondrial PE- and CL-trafficking proteins and prior knowledge of their biosynthetic pathways have provided targets for precisely manipulating nonbilayer phospholipid levels in the mitochondrial membranes in vivo. Thus, the genetic mutants of these pathways could be valuable tools in illuminating molecular functions and biophysical properties of nonbilayer phospholipids in driving mitochondrial bioenergetics and dynamics.
Topics: Animals; Cardiolipins; Electron Transport; Electron Transport Chain Complex Proteins; Humans; Mitochondria; Mitochondrial Proteins; Phosphatidylethanolamines; Protein Transport
PubMed: 29067684
DOI: 10.1002/1873-3468.12887 -
Oxidative Medicine and Cellular... 2017Phosphatidylethanolamine (PE) is the second most abundant phospholipid in mammalian cells. PE comprises about 15-25% of the total lipid in mammalian cells; it is... (Review)
Review
Phosphatidylethanolamine (PE) is the second most abundant phospholipid in mammalian cells. PE comprises about 15-25% of the total lipid in mammalian cells; it is enriched in the inner leaflet of membranes, and it is especially abundant in the inner mitochondrial membrane. PE has quite remarkable activities: it is a lipid chaperone that assists in the folding of certain membrane proteins, it is required for the activity of several of the respiratory complexes, and it plays a key role in the initiation of autophagy. In this review, we focus on PE's roles in lipid-induced stress in the endoplasmic reticulum (ER), Parkinson's disease (PD), ferroptosis, and cancer.
Topics: Animals; Disease; Endoplasmic Reticulum Stress; Ethanolamine; Health; Humans; Models, Biological; Phosphatidylethanolamines
PubMed: 28785375
DOI: 10.1155/2017/4829180 -
Biochimica Et Biophysica Acta.... Apr 2017It was first discovered in 1992 that P-glycoprotein (Pgp, ABCB1), an ATP binding cassette (ABC) transporter, can transport phospholipids such as phosphatidylcholine,... (Review)
Review
It was first discovered in 1992 that P-glycoprotein (Pgp, ABCB1), an ATP binding cassette (ABC) transporter, can transport phospholipids such as phosphatidylcholine, -ethanolamine and -serine as well as glucosylceramide and glycosphingolipids. Subsequently, many other ABC transporters were identified to act as lipid transporters. For substrate transport by ABC transporters, typically a classic, alternating access model with an ATP-dependent conformational switch between a high and a low affinity substrate binding site is evoked. Transport of small hydrophilic substrates can easily be imagined this way, as the molecule can in principle enter and exit the transporter in the same orientation. Lipids on the other hand need to undergo a 180° degree turn as they translocate from one membrane leaflet to the other. Lipids and lipidated molecules are highly diverse, so there may be various ways how to achieve their flipping and flopping. Nonetheless, an increase in biophysical, biochemical and structural data is beginning to shed some light on specific aspects of lipid transport by ABC transporters. In addition, there is now abundant evidence that lipids affect ABC transporter conformation, dynamics as well as transport and ATPase activity in general. In this review, we will discuss different ways in which lipids and ABC transporters interact and how lipid translocation may be achieved with a focus on the techniques used to investigate these processes. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.
Topics: ATP Binding Cassette Transporter, Subfamily B; Binding Sites; Biological Transport; Fatty Acids; Gene Expression; Humans; Models, Molecular; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylserines; Protein Binding; Protein Isoforms; Substrate Specificity
PubMed: 27693344
DOI: 10.1016/j.bbamem.2016.09.023 -
Biochimica Et Biophysica Acta.... Jan 2020The turnover of phospholipids plays an essential role in membrane lipid homeostasis by impacting both lipid head group and acyl chain composition. This review focusses... (Review)
Review
The turnover of phospholipids plays an essential role in membrane lipid homeostasis by impacting both lipid head group and acyl chain composition. This review focusses on the degradation and acyl chain remodeling of the major phospholipid classes present in the ER membrane of the reference eukaryote Saccharomyces cerevisiae, i.e. phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Phospholipid turnover reactions are introduced, and the occurrence and important functions of phospholipid remodeling in higher eukaryotes are briefly summarized. After presenting an inventory of established mechanisms of phospholipid acyl chain exchange, current knowledge of phospholipid degradation and remodeling by phospholipases and acyltransferases localized to the yeast ER is summarized. PC is subject to the PC deacylation-reacylation remodeling pathway (PC-DRP) involving a phospholipase B, the recently identified glycerophosphocholine acyltransferase Gpc1p, and the broad specificity acyltransferase Ale1p. PI is post-synthetically enriched in C18:0 acyl chains by remodeling reactions involving Cst26p. PE may undergo turnover by the phospholipid: diacylglycerol acyltransferase Lro1p as first step in acyl chain remodeling. Clues as to the functions of phospholipid acyl chain remodeling are discussed.
Topics: Acylation; Animals; Endoplasmic Reticulum; Humans; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylinositols; Phospholipids; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 31146038
DOI: 10.1016/j.bbalip.2019.05.006 -
The Journal of Cell Biology Mar 2022Glycosylphosphatidylinositol (GPI) is a glycolipid membrane anchor found on surface proteins in all eukaryotes. It is synthesized in the ER membrane. Each GPI anchor...
Glycosylphosphatidylinositol (GPI) is a glycolipid membrane anchor found on surface proteins in all eukaryotes. It is synthesized in the ER membrane. Each GPI anchor requires three molecules of ethanolamine phosphate (P-Etn), which are derived from phosphatidylethanolamine (PE). We found that efficient GPI anchor synthesis in Saccharomyces cerevisiae requires Csf1; cells lacking Csf1 accumulate GPI precursors lacking P-Etn. Structure predictions suggest Csf1 is a tube-forming lipid transport protein like Vps13. Csf1 is found at contact sites between the ER and other organelles. It interacts with the ER protein Mcd4, an enzyme that adds P-Etn to nascent GPI anchors, suggesting Csf1 channels PE to Mcd4 in the ER at contact sites to support GPI anchor biosynthesis. CSF1 has orthologues in Caenorhabditis elegans (lpd-3) and humans (KIAA1109/TWEEK); mutations in KIAA1109 cause the autosomal recessive neurodevelopmental disorder Alkuraya-Kučinskas syndrome. Knockout of lpd-3 and knockdown of KIAA1109 reduced GPI-anchored proteins on the surface of cells, suggesting Csf1 orthologues in human cells support GPI anchor biosynthesis.
Topics: Autophagy; Endoplasmic Reticulum; Glycosylphosphatidylinositols; Mitochondria; Phosphatidylethanolamines; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35015055
DOI: 10.1083/jcb.202111095 -
Mitochondrion Nov 2019Mitochondria, the double membrane-walled powerhouses of the eukaryotic cell, are also the seats of synthesis of two critical yet prevalent nonbilayer-prone... (Review)
Review
Mitochondria, the double membrane-walled powerhouses of the eukaryotic cell, are also the seats of synthesis of two critical yet prevalent nonbilayer-prone phospholipids, namely phosphatidylethanolamine (PE) and cardiolipin (CL). Besides their established biochemical roles in the regulation of partner protein function, PE and CL are also key protagonists in the biophysics of mitochondrial membrane remodeling and dynamics. In this review, we address lipid geometry and behavior at the single-molecule level as well as their intimate coupling to whole organelle morphology and remodeling during the concerted events of mitochondrial fission. We present evidence from recent experimental measurements ably supported and validated by computational modeling studies to support our notion that conical lipids play a catalytic as well as a structural role in mitochondrial fission.
Topics: Animals; Cardiolipins; Humans; Mitochondria; Mitochondrial Dynamics; Mitochondrial Membranes; Phosphatidylethanolamines
PubMed: 31351921
DOI: 10.1016/j.mito.2019.07.010 -
Biochimica Et Biophysica Acta May 2016The bacterial membrane provides a target for antimicrobial peptides. There are two groups of bacteria that have characteristically different surface membranes. One is... (Review)
Review
The bacterial membrane provides a target for antimicrobial peptides. There are two groups of bacteria that have characteristically different surface membranes. One is the Gram-negative bacteria that have an outer membrane rich in lipopolysaccharide. Several antimicrobials have been found to inhibit the synthesis of this lipid, and it is expected that more will be developed. In addition, antimicrobial peptides can bind to the outer membrane of Gram-negative bacteria and block passage of solutes between the periplasm and the cell exterior, resulting in bacterial toxicity. In Gram-positive bacteria, the major bacterial lipid component, phosphatidylglycerol can be chemically modified by bacterial enzymes to convert the lipid from anionic to cationic or zwitterionic form. This process leads to increased levels of resistance of the bacteria against polycationic antimicrobial agents. Inhibitors of this enzyme would provide protection against the development of bacterial resistance. There are antimicrobial agents that directly target a component of bacterial cytoplasmic membranes that can act on both Gram-negative as well as Gram-positive bacteria. Many of these are cyclic peptides with a rigid binding site capable of binding a lipid component. This binding targets antimicrobial agents to bacteria, rather than being toxic to host cells. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.
Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cardiolipins; Cell Membrane; Cell Membrane Permeability; Gram-Negative Bacteria; Gram-Positive Bacteria; Lipid A; Lipopolysaccharides; Molecular Targeted Therapy; Phosphatidylethanolamines; Species Specificity
PubMed: 26514603
DOI: 10.1016/j.bbamem.2015.10.018