PHO 1: General and New Sources of Phospholipids and Applications
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Synthesis of Lysophospholipids
Molecules 2010, 15, 1354-1377; doi:10.3390/molecules15031354 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Synthesis of Lysophospholipids Paola D’Arrigo 1,2,* and Stefano Servi 1,2 1 Dipartimento di Chimica, Materiali ed Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy 2 Centro Interuniversitario di Ricerca in Biotecnologie Proteiche "The Protein Factory", Politecnico di Milano and Università degli Studi dell'Insubria, Via Mancinelli 7, 20131 Milano, Italy * Author to whom correspondence should be addressed; E-Mail: paola.d’[email protected]. Received: 17 February 2010; in revised form: 4 March 2010 / Accepted: 5 March 2010 / Published: 8 March 2010 Abstract: New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs) are very important in solving problems of membrane–chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs) using regiospecific enzymes such as phospholipases A1 (PLA1), A2 (PLA2) phospholipase D (PLD) and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo- enzymatic procedures leading to 1- and 2-LPLs will be described. -
The Gut Microbiome Modulates Gut–Brain Axis Glycerophospholipid
Molecular Psychiatry (2021) 26:2380–2392 https://doi.org/10.1038/s41380-020-0744-2 ARTICLE The gut microbiome modulates gut–brain axis glycerophospholipid metabolism in a region-specific manner in a nonhuman primate model of depression 1,2,3,4 5 1,2,3 4 1,2,3 1,2,3 Peng Zheng ● Jing Wu ● Hanping Zhang ● Seth W. Perry ● Bangmin Yin ● Xunmin Tan ● 1,2,3 6 1,2,3 1,2,3 5 4 4 Tingjia Chai ● Weiwei Liang ● Yu Huang ● Yifan Li ● Jiajia Duan ● Ma-Li Wong ● Julio Licinio ● Peng Xie1,2,3 Received: 27 December 2019 / Revised: 9 April 2020 / Accepted: 20 April 2020 / Published online: 6 May 2020 © The Author(s), under exclusive licence to Springer Nature Limited 2020 Abstract Emerging research demonstrates that microbiota-gut–brain (MGB) axis changes are associated with depression onset, but the mechanisms underlying this observation remain largely unknown. The gut microbiome of nonhuman primates is highly similar to that of humans, and some subordinate monkeys naturally display depressive-like behaviors, making them an ideal model for studying these phenomena. Here, we characterized microbial composition and function, and gut–brain metabolic 1234567890();,: 1234567890();,: signatures, in female cynomolgus macaque (Macaca fascicularis) displaying naturally occurring depressive-like behaviors. We found that both microbial and metabolic signatures of depressive-like macaques were significantly different from those of controls. The depressive-like monkeys had characteristic disturbances of the phylum Firmicutes. In addition, the depressive-like macaques were characterized by changes in three microbial and four metabolic weighted gene correlation network analysis (WGCNA) clusters of the MGB axis, which were consistently enriched in fatty acyl, sphingolipid, and glycerophospholipid metabolism. -
Phosphatidic Acid: Biosynthesis, Pharmacokinetics, Mechanisms of Action and Effect on Strength and Body Composition in Resistance-Trained Individuals Peter Bond
Bond Nutrition & Metabolism (2017) 14:12 DOI 10.1186/s12986-017-0166-6 REVIEW Open Access Phosphatidic acid: biosynthesis, pharmacokinetics, mechanisms of action and effect on strength and body composition in resistance-trained individuals Peter Bond Abstract The mechanistic target of rapamycin complex 1 (mTORC1) has received much attention in the field of exercise physiology as a master regulator of skeletal muscle hypertrophy. The multiprotein complex is regulated by various signals such as growth factors, energy status, amino acids and mechanical stimuli. Importantly, the glycerophospholipid phosphatidic acid (PA) appears to play an important role in mTORC1 activation by mechanical stimulation. PA has been shown to modulate mTOR activity by direct binding to its FKBP12-rapamycin binding domain. Additionally, it has been suggested that exogenous PA activates mTORC1 via extracellular conversion to lysophosphatidic acid and subsequent binding to endothelial differentiation gene receptors on the cell surface. Recent trials have therefore evaluated the effects of PA supplementation in resistance-trained individuals on strength and body composition. As research in this field is rapidly evolving, this review attempts to provide a comprehensive overview of its biosynthesis, pharmacokinetics, mechanisms of action and effect on strength and body composition in resistance-trained individuals. Keywords: Phosphatidic acid, mTORC1, Muscle hypertrophy Background complex and functions as a serine/threonine protein kin- Skeletal muscle mass comprises roughly half of our body ase belonging to the phosphatidylinositol-3 kinase mass and is essential for locomotion, heat production (PI3K)-related kinase (PIKK) superfamily [7]. mTORC1 during periods of cold stress and overall metabolism [1]. acts as a signal integrator of various environmental cues Skeletal muscle mass can be increased by mechanical and controls protein synthesis, specifically the process of loading such as a resistance exercise program [2]. -
Control of Free Arachidonic Acid Levels by Phospholipases A2 And
Control of Free Arachidonic Acid Levels by Phospholipases A2 and Lysophospholipid Acyltransferases Gema Pérez-Chacón, Alma M. Astudillo, David Balgoma, María A. Balboa, and Jesús Balsinde* Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain, and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain *Corresponding author. Phone, +34-983-423-062; Fax, +34-983-184-800; e-mail: [email protected] Keywords: Arachidonic Acid; Phospholipase A2; Free fatty acid; Eicosanoids; Acyltransferase; Phospholipid Remodeling. Running Title: Control of Arachidonic Acid Levels 1 Abstract Arachidonic acid (AA) and its oxygenated derivatives, collectively known as the eicosanoids, are key mediators of a wide variety of physiological and pathophysiological states. AA, obtained from the diet or synthesized from linoleic acid, is rapidly incorporated into cellular phospholipids by the concerted action of arachidonoyl-CoA synthetase and lysophospholipid acyl transferases. Under the appropriate conditions, AA is liberated from its phospholipid storage sites by the action of one or various phospholipase A2 enzymes. Thus, cellular availability of AA, and hence the amount of eicosanoids produced, depends on an exquisite balance between phospholipid reacylation and hydrolysis reactions. This review focus on the enzyme families that are involved in these reactions in resting and stimulated cells. Abbreviations AA, arachidonic -
Phosphatidylcholine Treatment to Induce Lipolysis
Journal Innoventions PhosphatidylcholineBlackwell Publishing Inc treatment to induce lipolysis Franz Hasengschwandtner Therapy-Clinic Center, Bad Leonfelden, Austria Summary The medicine Lipostabil N® has been in widespread use in Europe since 2002 by doctors working in the field of esthetics to achieve a reduction in the volume of smaller fat deposits by means of injections into the subcutaneous fatty tissue. The lipases released from the adipocytes by means of phosphatidylcholine produce a local breakdown of fat that is then discharged over the liver and metabolized via beta- oxidation. The medicine has been authorized for intravenous use in the prophylaxis and therapy of fat embolisms and liver diseases. Keywords: detergents, lecithins, lipolysis, phosphatidylcholine her lower eye pads by injecting phosphatidylcholine History under her eyes.2 In Europe, further study of the medica- Phosphatidylcholine was first isolated in Odessa, Ukraine ment started in 2001, and the first treatments were made some 50 years ago. This was followed by further research by the author in late 2002. In 2003 “Network Lipolysis” in Germany and Russia. It has been marketed by Sanofi- was founded in Germany by Ulrich Bunzek and Dirk Aventis for over 30 years and, at present, the substance Brandl and with this started the European investigation phosphatidylcholine is registered in 53 countries. Its main of the scientific background of this new esthetic therapy. application nowadays lies in the intravenous treatment Phosphatidylcholine makes up the largest choline and prevention of fat embolisms in polytraumatized (lecithin) reservoir in the body and is found in bile. It patients in the treatment of metabolic disorders and as a facilitates the emulsification of fat into the tiniest particles liver-protecting substance. -
Large-Scale Lipidomic Profiling Identifies Novel Potential
Kim et al. Vet Res (2021) 52:105 https://doi.org/10.1186/s13567-021-00975-1 RESEARCH ARTICLE Open Access Large-scale lipidomic profling identifes novel potential biomarkers for prion diseases and highlights lipid raft-related pathways Yong‑Chan Kim1,2, Junbeom Lee3, Dae‑Weon Lee3,4* and Byung‑Hoon Jeong1,2* Abstract Prion diseases are transmissible spongiform encephalopathies induced by the abnormally‑folded prion protein (PrPSc), which is derived from the normal prion protein (PrPC). Previous studies have reported that lipid rafts play a pivotal role in the conversion of PrPC into PrPSc, and several therapeutic strategies targeting lipids have led to prolonged survival times in prion diseases. In addition, phosphatidylethanolamine, a glycerophospholipid member, accelerated prion disease progression. Although several studies have shown that prion diseases are signifcantly associated with lipids, lipidomic analyses of prion diseases have not been reported thus far. We intraperitoneally injected phosphate‑ bufered saline (PBS) or ME7 mouse prions into mice and sacrifced them at diferent time points (3 and 7 months) post‑injection. To detect PrPSc in the mouse brain, we carried out western blotting analysis of the left hemisphere of the brain. To identify potential novel lipid biomarkers, we performed lipid extraction on the right hemisphere of the brain and liquid chromatography mass spectrometry (LC/MS) to analyze the lipidomic profling between non‑infected mice and prion‑infected mice. Finally, we analyzed the altered lipid‑related pathways by a lipid pathway enrichment analysis (LIPEA). We identifed a total of 43 and 75 novel potential biomarkers at 3 and 7 months in prion‑infected mice compared to non‑infected mice, respectively. -
Ether Lipid and Sphingolipid Expression Patterns Are G-Protein Coupled
bioRxiv preprint doi: https://doi.org/10.1101/2020.07.20.212894; this version posted July 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Ether lipid and sphingolipid expression patterns are G-protein coupled 2 estrogen receptor 1-dependently altered in breast cancer cells 3 Lisa Hahnefeld1, Lisa Gruber1, Nina Schömel1, Caroline Fischer1, Peter Mattjus2, Robert 4 Gurke1,3, Martina Beretta4, Nerea Ferreirós1, Gerd Geisslinger1,3, Marthe-Susanna Wegner1,4 5 1pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang 6 Goethe University, Theodor Stern-Kai 7, 60590 Frankfurt am Main, Germany. 7 2Åbo Akademi University, Biochemistry, Faculty of Science and Engineering Artillerigatan 6A, 8 III, BioCity FI-20520 Turku, Finland. 9 3Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for 10 Translational Medicine and Pharmacology TMP, Theodor Stern-Kai 7, 60590 Frankfurt am 11 Main, Germany. 12 4School of Biotechnology and Biomolecular Sciences, University of New South Wales, 13 Sydney, New South Wales 2052, Australia. 14 15 16 17 18 19 20 21 22 Corresponding author: 23 24 Marthe-Susanna Wegner 25 School of Biotechnology & Biomolecular Sciences 26 UNSW SYDNEY NSW 2052 AUTRALIA 27 Phone: +61 (2) 9385 6516 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.20.212894; this version posted July 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Human Monocytes Arachidonic Acid Reacylation Reactions In
The Journal of Immunology Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes Gema Pe´rez-Chaco´n, Alma M. Astudillo, Violeta Ruipe´rez, Marı´a A. Balboa, and Jesu´s Balsinde Cellular availability of free arachidonic acid (AA) is an important step in the production of pro- and anti-inflammatory eicosanoids. Control of free AA levels in cells is carried out by the action of phospholipase A2s and lysophospholipid acyltransferases, which are responsible for the reactions of deacylation and incorporation of AA from and into the sn-2 position of phospholipids, respectively. In this work, we have examined the pathways for AA incorporation into phospholipids in human monocytes stimulated by zymosan. Our data show that stimulated cells exhibit an enhanced incorporation of AA into phospholipids that is not secondary to an increased availability of lysophospholipid acceptors due to phospholipase A2 activation but rather reflects the receptor- regulated nature of the AA reacylation pathway. In vitro activity measurements indicate that the receptor-sensitive step of the AA reacylation pathway is the acyltransferase using lysophosphatidylcholine (lysoPC) as acceptor, and inhibition of the enzyme lysoPC acyltransferase 3 by specific small interfering RNA results in inhibition of the stimulated incorporation of AA into phospholipids. Collectively, these results define lysoPC acyltransferase 3 as a novel-signal–regulated enzyme that is centrally implicated in limiting free AA levels in activated cells. The Journal of Immunology, 2010, 184: 1071–1078. rachidonic acid (AA) is the common precursor of the acid release by constitutive iPLA2 is lesser than the rate of its eicosanoids, a family of biologically active lipid medi- reacylation back into PLs, no net accumulation of free fatty acid A ators, which play key roles in inflammatory processes and occurs. -
Lecithins from Vegetable, Land, and Marine Animal Sources and Their Potential Applications for Cosmetic, Food, and Pharmaceutical Sectors
cosmetics Review Lecithins from Vegetable, Land, and Marine Animal Sources and Their Potential Applications for Cosmetic, Food, and Pharmaceutical Sectors Maria J. Alhajj , Nicolle Montero , Cristhian J. Yarce and Constain H. Salamanca * Laboratorio de Diseño y Formulación de Productos Químicos y Derivados, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Naturales, Universidad ICESI, Calle 18 No. 122-135, 760035 Cali, Colombia; [email protected] (M.J.A.); [email protected] (N.M.); [email protected] (C.J.Y.) * Correspondence: [email protected]; Tel.: +57-312-223-8310 Received: 29 September 2020; Accepted: 4 November 2020; Published: 9 November 2020 Abstract: The aim of this work was to review the reported information about the phospholipid composition of lecithins derived from several natural sources (lipids of plant, animal, and marine origin) and describe their main applications for the cosmetic, food, and pharmaceutical sectors. This study was carried out using specialized search engines and according to the following inclusion criteria: (i) documents published between 2005 and 2020, (ii) sources of lecithins, (iii) phospholipidic composition of lecithins, and (iv) uses and applications of lecithins. Nevertheless, this work is presented as a narrative review. Results of the review indicated that the most studied source of lecithin is soybean, followed by sunflower and egg yolk. Contrarily, only a few numbers of reports focused on lecithins derived from marine animals despite the relevance of this source in association with an even higher composition of phospholipids than in case of those derived from plant sources. Finally, the main applications of lecithins were found to be related to their nutritional aspects and ability as emulsion stabilizers and lipid component of liposomes. -
Discovery of a Lysophospholipid Acyltransferase Family Essential for Membrane Asymmetry and Diversity
Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity Daisuke Hishikawa*, Hideo Shindou*, Saori Kobayashi*, Hiroki Nakanishi†, Ryo Taguchi†‡, and Takao Shimizu*§ Departments of *Biochemistry and Molecular Biology and †Metabolome, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Tokyo 113-0033, Japan; and ‡Core Research for Evolutional Science and Technology of the Japan Science and Technology Agency, Kawaguchi, Saitama 332-8613, Japan Communicated by Yoshito Kaziro, Kyoto University, Kyoto, Japan, December 29, 2007 (received for review October 21, 2007) All organisms consist of cells that are enclosed by a cell membrane are carried out in a variety of tissues, information on the enzyme containing bipolar lipids and proteins. Glycerophospholipids are im- molecules involved in the phospholipid remodeling is limited. portant not only as structural and functional components of cellular We cloned lyso-PA acyltransferase ␣ (LPAAT␣) and found that membrane but also as precursors of various lipid mediators. Polyun- the enzyme used LPA as an acyl acceptor (11). Whereas the saturated fatty acids comprising arachidonic acid or eicosapentaenoic recombinant LPAAT␣ was shown to use various fatty acyl-CoAs as acid are located at sn-2 position, but not at sn-1 position of glycero- acyl donors, no lysophospholipid other than LPA was found to phospholipids in an asymmetrical manner. In addition to the asym- serve as an acceptor. Several LPLATs, including LPAAT␣ and , metry, the membrane diversity is important for membrane fluidity lyso-PG acyltransferase (LPGAT), and lyso-CL acyltransferase and curvature. To explain the asymmetrical distribution of fatty acids, (ALCAT), have been cloned in the last decade, and putative the rapid turnover of sn-2 position was proposed in 1958 by Lands LPAATs (␥, ␦, , , and ) and tafazzin have been reported (12–19). -
Enhanced Fatty Acid Scavenging and Glycerophospholipid Metabolism Accompany Melanocyte Neoplasia Progression in Zebrafish Fiona Henderson1,2, Hannah R
Published OnlineFirst March 12, 2019; DOI: 10.1158/0008-5472.CAN-18-2409 Cancer Metabolism and Chemical Biology Research Enhanced Fatty Acid Scavenging and Glycerophospholipid Metabolism Accompany Melanocyte Neoplasia Progression in Zebrafish Fiona Henderson1,2, Hannah R. Johnston3, Andrew P. Badrock3, Emrys A. Jones4, Duncan Forster1, Raghavendar T. Nagaraju3, Christos Evangelou3, Jivko Kamarashev5, Michael Green1, Michael Fairclough1, Irene Barinaga-Rementeria Ramirez3, Shuning He6,7, B. Ewa Snaar-Jagalska6, Katherine Hollywood8, Warwick B. Dunn8,9, Herman P. Spaink6, Michael P. Smith3, Paul Lorigan10, Emmanuelle Claude4, Kaye J. Williams2, Adam W. McMahon1, and Adam Hurlstone3 Abstract Alterations in lipid metabolism in cancer cells impact cell rated by DESI-MS, which again revealed heterogeneous phos- structure, signaling, and energy metabolism, making lipid pholipid composition in tumors. Overexpression of the gene metabolism a potential diagnostic marker and therapeutic encoding lipoprotein lipase (LPL), which was upregulated in target. In this study, we combined PET, desorption electro- zebrafish melanocyte tumor nodules and expressed in the spray ionization-mass spectrometry (DESI-MS), nonimaging majority of human melanomas, accelerated progression of MS, and transcriptomic analyses to interrogate changes in oncogenic RAS-driven melanocyte neoplasia in zebrafish. lipid metabolism in a transgenic zebrafish model of onco- Depletion or antagonism of LPL suppressed human melanoma genic RAS-driven melanocyte neoplasia progression. Exoge- -
Lipids Lipid Nomenclature
Chapter 8 questions: 5,6,7,10,15,16,17,18,20,21,22. Also, how does the fact that many glycerophospholipids are made of unsaturated fatty acids affect the physical properties of the fatty acids and the membrane lipids to which they are esterified? Lipids •Lipids in biological systems can be hydrophobic or amphipathic. •Hydrophobic lipids, not surprisingly, are hydrophobic. •Amphipathic lipids have a polar group (head) and a hydrophobic group (tail) and are utilized in membranes. If the polar group has a carboxylic acid moiety, this is a fatty acid. •Fatty acids can be saturated or unsaturated. •Saturated fatty acids have only single carbon-carbon bonds. •Unsaturated fatty acids have at least one double carbon-carbon bond. •Monoumsaturated fatty acids have one double carbon-carbon bond •Polyunsaturated fatty acids have more than one double carbon-carbon bond. Lipid nomenclature • Lipids have common names , e.g., myristic acid. • The systematic name takes into account the number of carbons in the hydrophobic chain, e.g., tetradodecanoic acid for the 14 carbons of myristic acid. • The symbol nomenclature takes into account the number of carbons in the chain and the number of unsaturated bonds. Myristic acids is described by 14:0, meaning there are 14 carbons and no unsaturated bonds. • Linoleic acid has 18 carbons and two double bonds, one between C9 and C10, and the other between C12 and C13. The systematic name is 9,12-octadecadienoic acid. The symbol nomenclature is 18:2 (9,12). • Carbon counting starts at the carboxylic acid carbon in the delta counting system. Carbon counting starts at the carbon end in the omega counting system.