Chemistry
Sphingolipids
Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a fatty acid, and a polar head group. They are important components of cell membranes and play roles in signaling pathways. Sphingolipids are involved in various cellular processes, including cell growth, differentiation, and apoptosis. Their diverse structures and functions make them essential for maintaining cell integrity and regulating cellular processes.
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10 Key excerpts on "Sphingolipids"
eBook - ePub- Jose M. Mato(Author)
- 2018(Publication Date)
- CRC Press(Publisher)
Sphingolipids in Cellular SignalingJosé M. MatoTable of Contents
I. Introduction II. Biological Functions of Glycolipids III. Biological Functions of Sphingosine IV. Mechanism of Action of Sphingosine References I. IntroductionThe simplest class of sphingohpids are sphingomyelins, a major component of animal cell membranes and serum lipoproteins. The structure of sphingomyelin, N -acylsphingosine-1-phosphorylcholine or ceramide-l-phosphorylcholine, is shown in Figure 1 .1 , 2 Like the phosphatidylcholine molecules, sphingomyelins consist of two hydrophobic groups (the sphingosine group and the acyl group) and a phosphorylcholine group. Sphingomyelins occurring in biological membranes differ in the nature of the sphingosine base and the acyl group. The most common sphingosine is the 18-carbon aminediol, l,3-dihydroxy-2-amino-4-octodecene. This molecule has a trans double bond between carbons 4 and 5. The dihydro derivative of this base, l,3-dihydroxy-2-amino octadecane, is also present in biological membranes in small amounts, and is known by the name of sphinganine.3 - 5 Phytosphingosine (l,3,4-hydroxy-2-aminooctadecane) has also been detected in bovine kidney.6 These molecules are collectively referred to as long-chain sphingoid bases. The fatty acids commonly found in sphingomyelin are palmitic (16:0), nervonoyl (24:1), 22:0, and 24:0.7 In brain, the most common fatty acid found is stearic acid (18:0), nervonoyl (24:1) and 24:0 being less common.8 An interesting difference in the fatty acid composition of phosphoglycerolipids is the presence of longer fatty acid molecules (22:0, 24:0, and 24:1) in sphingomyelins. Little is known about the factors that control the alkyl chain length and the degree of unsaturation of the Sphingolipids. Differences in the long-chain sphingoid base composition of sphingomyelin have been observed in rats bearing Morris hepatoma 7777, which suggests the existence of variations in the alkyl composition of Sphingolipids in neoplasia.9
- Dennis E. Vance, J.E. Vance(Authors)
- 1996(Publication Date)
- Elsevier Science(Publisher)
Chapter 12Sphingolipids: metabolism and cell signalling
Alfred H. Merrill, Jr Department of Biochemistry, Emory University, Atlanta, GA 30322Charles C. Sweeley Department of Biochemistry, Michigan State University, East Lansing, MI 48824, USA1 Introduction
Sphingolipids are nearly ubiquitous constituents of membranes in animals, plants, fungi, yeast, and some prokaryotic organisms and viruses. They were first described in a remarkable book, A Treatise on the Chemical Constitution of Brain , published by Johann L.W. Thudichum in 1884 [1] . Among the novel compounds discovered and named by Thudichum were sphingomyelin, cerebroside, and cerebrosulfatide (Fig. 1 ). Hydrolysis of these lipids produced a compound that Thudichum stated “…is of an alkaloidal nature, and to which, in commemoration of the many enigmas which it has presented to the inquirer, I have given the name of Sphingosin .” Thus, this class of lipids became known as sphingo lipids due to their common sphingosine backbone (Fig. 1 ).Fig. 1 Structures of sphingosine, ceramide, sphingomyelin, a cerebroside (galactosylceramide) and cerebrosulfatide from human brain.1.1 Biological significance of Sphingolipids
The complexity of Sphingolipids, plus the impression that they were mainly found in neuronal systems, contributed to the relative neglect of this class of compounds for much of the century following their discovery. Subsequent interest in Sphingolipids has come in two waves. The first was the finding of abnormal levels of Sphingolipids in liver, spleen, brain and other organs in several human diseases, including Niemann-Pick disease (sphingomyelin) and Tay–Sachs disease (gangliosides). Elucidation of the genetic defects that cause these diseases [2 –6 ] led not only to methods for the screening of families at risk, but also, to efforts to correct the disorders by enzyme replacement [7]
- Neale Ridgway, Roger McLeod(Authors)
- 2015(Publication Date)
- Elsevier Science(Publisher)
Chapter 10Sphingolipids
Anthony H. Futerman Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, IsraelAbstract
Sphingolipids are ubiquitous components of eukaryotic cell membranes and have been widely studied over the past couple of decades due to the discovery of their involvement in a wide range of biological processes. This chapter focuses on the structure, biosynthesis and degradation of Sphingolipids, with particular emphasis on recent studies documenting the huge numbers of individual sphingolipid structures that are based on variation in both the sphingolipid backbone and the head group. Attention is also paid to the roles of Sphingolipids in signalling pathways with emphasis on sphingosine 1-phosphate and on ceramide. The significance of Sphingolipids in human diseases is highlighted, as Sphingolipids are now known to play a role in conditions ranging in diversity from inflammation and infection, to cancer, psychiatric disorders and neurological and immunological diseases. Thus, Sphingolipids have been repositioned as fundamental players in the regulation of human health and disease.AbbreviationsKeywords
Ceramide; GlycoSphingolipids; Human disease; Lipid biosynthesis; Lipid degradation; Lipid signalling; Rafts; Sphingosine 1-phosphateASM Acid sphingomyelinase CerS Ceramide synthases CERT Ceramide transport protein CNS Central nervous system DAG Diacylglycerol ER Endoplasmic reticulum FAPP2 Four-phosphate adaptor protein 2 FFAT Two-phenylalanines in an acidic tract GalCer Galactosylceramide GlcCer Glucosylceramide GSL Glycosphingolipid HSAN1 Hereditary sensory neuropathy type I 3KSR 3-Ketosphinganine reductase LCB Long chain base LSD Lysosomal storage disease MLD Metachromatic leukodystrophy PC Phosphatidylcholine PH Pleckstrin homology PI Phosphatidylinositol SAP Sphingolipid activator protein S1P Sphingosine 1-phosphate
- Fereidoon Shahidi(Author)
- 2006(Publication Date)
- CRC Press(Publisher)
CONTENTS 6.1 Introduction ........................................................................................................................... 127 6.2 Structure of Sphingolipids .................................................................................................... 128 6.3 Sphingolipids in Foods ......................................................................................................... 129 6.4 Sphingolipids Analysis ......................................................................................................... 132 References ...................................................................................................................................... 134 6.1 INTRODUCTION Sphingolipids are found in all eucaryotic cells, but are especially abundant in the plasma membrane and related cell membranes, such as endoplasmic reticulum, golgi membranes, and lysosomes. They play an important role in maintaining membrane structure, and participate in intracellular sig-naling 1 . As receptors and ligands, they are involved in interactions between cells, and cells and matrix; they also serve as a binding site for toxins of bacterial and nonbacterial origin and hormones and viruses, among others 2,3 . Sphingolipids are a major topic of current research for several reasons. Firstly, Sphingolipids are mediators of the signaling pathway of growth factors (e.g., platelet-derived growth factor), cytokines (e.g., tumor necrosis factor), and chemotherapeutics, and play an important role in regu-lation of cell growth, differentiation, and death. The hydrolysis products of Sphingolipids, ceramides, sphingosine, and sphingosine-1-phosphate, are highly bioactive compounds that can, as a potent mitogen (sphingosine 1-phosphate, sphinganine 1-phosphate), act as lipid “second messengers” in the signal transduction pathways that either induce apoptosis (sphingosine, sphinganine, ceramides) or inhibit apoptosis 2,4 .
eBook - PDF- Anthony H. Futerman, Ari Zimran(Authors)
- 2006(Publication Date)
- CRC Press(Publisher)
CELLULAR BIOLOGY OF Sphingolipids Much has been written about the functions of Sphingolipids over the last 20 years. A comprehensive treatment of the role of Sphingolipids in cellular biology 118 GAUCHER DISEASE and the pathogenesis of disease is well beyond the scope of this brief review. Much of this work has focused on the role of Sphingolipids in cell signaling processes. Collectively one may divide these studies into three general groups. These groups include Sphingolipids as intracellular second messengers, Sphingolipids as cell dif-ferentiation markers and receptors, and Sphingolipids as modulators of signal trans-duction. Ceramide has been identified as a potential signal for apoptosis, 10 cell growth arrest, 11 and stress responses 60 for many years. Traditionally ceramide has been viewed as a second messenger akin to diglyceride and protein kinase C. Unlike diglyceride, however, the identification of a single class of cellular targets for cera-mide action has been difficult. Cellular targets that have been identified as sites for ceramide include but are not limited to PP2A, 61 PP1, 62 c-Raf, 63 PKC ζ , 64 and KSR1. 65 Sphingosine-1-phosphate has been identified as a bioactive lipid that functions as an extracellular ligand and an intracellular second messenger. 66 S1P binds to one of five G protein coupled Edg/S1P receptors. The biological responses are mediated in part through the mobilization of intracellular calcium. These responses are pro-found and vary from cell proliferation, immune cell trafficking, and vascular per-meability. 67 Ceramide-1-phosphate appears to act intracellularly. Ceramide 1-phos-phate has been associated with a number of biological activities. These activities include mitogenesis, membrane fusion (including that associated with phagolysos-ome formation), 68 calcium signaling, 69 and the regulation of phospholipase A2. 70 GlycoSphingolipids have long been studied by cell biologists.
eBook - PDF- Li Feng, Glenn D. Prestwich(Authors)
- 2005(Publication Date)
- CRC Press(Publisher)
150 Functional Lipidomics kinases. S1P lyase then cleaves this molecule to generate ethanolamine phosphate and a fatty aldehyde. The study of Sphingolipids has witnessed a dramatic resurgence with the increas-ing appreciation of the various functions of these molecules. In membrane bilayer structure and function, Sphingolipids, especially sphingomyelin and perhaps gly-coSphingolipids, are involved in organizing membranes into more rigid micro-domains that include rafts and caveolae. These specialized membrane structures are increasingly appreciated to play critical roles in transmembrane signal transduction and in endocytosis. In addition, it is now well established that the levels of several Sphingolipids, including sphingosine, ceramide, ceramide-1-phosphate, and S1P, are regulated and that these molecules function as bioactive lipids involved in various processes of signal transduction and cell regulation. Ceramide levels can be regulated by at least two pathways (Figure 7.2a). In the fi rst pathway, neutral and acid sphingomyelinases respond to the action of various cytokines and stress signals, and their activation results in hydrolysis of sphingo-myelin and the generation of ceramide. Alternatively, substantial evidence also shows that increase in ceramide levels can be induced through the activation of the de novo pathway of sphingolipid synthesis (Figure 7.2a). In both cases, the generated cera-mide has been implicated in the regulation of a number of signaling pathways including activation of phosphatases and kinases that in turn couple the formation of ceramide to speci fi c cellular responses (Figure 7.2a). For example, activation of protein phosphatase 1 causes dephosphorylation of the retinoblastoma gene product (Rb), resulting in cell cycle arrest. Multiple mechanisms induce a proapoptotic response to ceramide, and these include dephosphorylation of the antiapoptotic proteins Bcl-2, Akt, and protein kinase C.
eBook - ePubFundamentals of Biochemistry, Integrated E-Text with E-Student Companion
Life at the Molecular Level
- Donald Voet, Judith G. Voet, Charlotte W. Pratt(Authors)
- 2017(Publication Date)
- Wiley(Publisher)
ceramides:Ceramides are the parent compounds of the more abundant Sphingolipids:- Sphingomyelins, the most common Sphingolipids, are ceramides bearing either a phosphocholine (Fig. 9-7) or a phosphoethanolamine head group, so they can also be classified as sphingophospholipids. They typically make up 10 to 20 mol % of plasma membrane lipids. Although sphingomyelins differ chemically from phosphatidylcholine and phosphatidylethanolamine, their conformations and charge distributions are quite similar (compare Figs. 9-4 and 9-7 ). The membranous myelin sheath that surrounds and electrically insulates many nerve cell axons is particularly rich in sphingomyelins (Fig. 9-8).A sphingomyelin. (a) Molecular formula. (b) Energy-minimized space-filling model with C green, H white, N blue, O red, and P orange. [Based on coordinates provided by Richard Venable and Richard Pastor, NIH, Bethesda, Maryland.]FIG. 9-7Electron micrograph of myelinated nerve fibers. This cross-sectional view shows the spirally wrapped membranes around each nerve axon. The myelin sheath may be 10–15 layers thick. Its high lipid content makes it an electrical insulator.FIG. 9-8
- Cerebrosides are ceramides with head groups that consist of a single sugar residue. These lipids are therefore glycoSphingolipids. Galactocerebrosides and glucocerebrosides are the most prevalent. Cerebrosides, in contrast to phospholipids, lack phosphate groups and hence are nonionic.
- Gangliosidesare the most complex glycoSphingolipids. They are ceramides with attached oligosaccharides that include at least one sialic acid residue. The structures of gangliosidesG,M 1G, andM 2G, three of the hundreds that are known, are shown inM 3Fig. 9-9
eBook - PDFChemistry for Today
General, Organic, and Biochemistry
- Spencer Seager, Michael Slabaugh, Maren Hansen, , Spencer Seager, Spencer Seager, Michael Slabaugh, Maren Hansen(Authors)
- 2021(Publication Date)
- Cengage Learning EMEA(Publisher)
A single fatty acid is also attached to the sphingosine, but an amide linkage is involved instead of an ester linkage. A number of sphingomyelins are known; they differ only in the fatty acid component. Large amounts of sphingomyelins are found in brain and nerve tissue and in the protective myelin sheath that surrounds nerves. sphingolipid A complex lipid containing the aminoalcohol sphingosine. A sphingomyelin S p h i n g o s i n e Fatty acid Phosphoric acid Choline Copyright 2022 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 598 Chapter 18 Example 18.8 Writing Sphingomyelin Structures In the following sphingomyelin structure, circle the component parts and label each cir- cle with one of these terms: sphingosine, fatty acid, phosphoric acid, or choline. CH(CH 2 ) 7 CH 3 O 2 CH CH 2 CH 3 (CH 2 ) 12 CH NH C O O P O (CH 2 ) 5 CH CH CH OH O CH 2 CH 2 N(CH 3 ) 3 1 Solution Using the structural guide above: CH(CH 2 ) 7 CH 3 O 2 CH CH 2 CH 3 (CH 2 ) 12 CH NH C O O P O (CH 2 ) 5 CH CH CH OH O CH 2 CH 2 N(CH 3 ) 3 1 phosphoric acid sphingosine choline fatty acid ✔ LEARNING CHECK 18.8 Write the structure of a sphingomyelin containing the fatty acid linoleic acid (shown below). CH 3 (CH 2 ) 4 (CH“CHCH 2 ) 2 (CH 2 ) 6 ¬COOH Glycolipids are another type of sphingolipid. Unlike sphingomyelins, however, these complex lipids contain carbohydrates (usually monosaccharides such as glucose or galactose). Glycolipids are often called cerebrosides because of their abundance in brain tissue.
eBook - PDF- P Karlson(Author)
- 1975(Publication Date)
- Academic Press(Publisher)
Sphingomyelins are also isolated as mixtures with different fatty acid components. Predominant among these are the acids with 24 C atoms lignoceric acid (saturated) and nervonic acid (one double bond). ΛΛΛΛΛΛΛΛΛ Ο / W V V W W W V 4. G L Y C O L I P I D S 261 4. Glycolipids Glycolipids have become increasingly prominent in the biochemical literature in recent years. They embody both a lipid and a carbohydrate moiety; the latter constitutes the hydrophilic pole of the molecule. Glyceroglycolipids have a relatively simple structure. They contain 1,2-diacylglycerol and a mono- or oligosaccharide bound glycosidically in position 3 of the glycerol. They are particularly abundant in bacteria, although they have been found in mammalian systems. GlycoSphingolipids are much more important. The main component is ceramide, which we have already encountered above. They can be categorized in one of three classes depending on the nature of the carbohydrate moiety : Neutral glycosphingo-lipids, sulfatides, and gangliosides. Cerebrosides are simple neutral glycoSphingolipids. Their carbohydrate is a monosaccharide. In cerebrosides derived from brain the monosaccharide is pre-dominantly galactose (see formula); in those derived from parenchymatous organs (liver, spleen, and others) it is mostly glucose. The fatty acids are saturated C 2 4 acids that occasionally feature a hydroxyl group in α position. Besides cerebrosides there are also compounds consisting of a ceramide and a di-, tri-, or tetrasaccharide. Such higher neutral glycoSphingolipids are widely distributed but exist only in very low concentrations. By their chemical structure they can be considered to be the neuraminate-free basic form of gangliosides ; there are also biogenetic relationships. Sulfatides are esters of sulfuric acid and neutral glycoSphingolipids. One very common type is derived from a galactocerebroside with a sulfate group at C-3 of galactose.
eBook - ePubPolar Lipids
Biology, Chemistry, and Technology
- Moghis U. Ahmad, Xuebing Xu(Authors)
- 2015(Publication Date)
- Academic Press and AOCS Press(Publisher)
J. Biol. Chem. . 2002; 277:6667–6675.Andressen, R. Ether Lipids in the Therapy of Cancer. Prog. Biochem. Pharmacol. . 1988; 22:118–131.Anliker, B., Chun, J. Lysophospholipid G Protein-coupled Receptors. J. Biol. Chem. . 2004; 279:20555–20558.Aoi, N. Soy Lysolecithin. Yukagaku . 1990; 39:10–15.Aoki, J., Taira, A., Takanezawa, Y., Kishi, Y., Hama, K., Kishimoto, T., Mizuno, K., Saku, K., Taguchi, R., Arai, H. Serum Lysophosphatidic Acid Is Produced through Diverse Phospholipase Pathways. J. Biol. Chem. . 2002; 277:48737–48744.Aoyagi, T., Nagahashi, M., Yamada, A., Takabe, K. The Role of Sphingosine 1-phosphate in Breast Cancer Tumor-induced Lymphangiogensis. Lymphatic Res. Biology . 2012; 10:97–106.Berdel, W. E., Andresen, R., Munder, P. G., Synthetic Alkyl-phospholipid Analogues; A New Class of Antitumor AgentsKuo J.F., ed. Phospholipids and Cellular Regulation. CRC Press, Boca Raton, FL, 1985;2:41–73.Bibak, N., Hajdu, J. A New Approach to the Synthesis of Lysophosphatidylcholines and Related Derivatives. Tetrahedron Lett. . 2003; 44:5875–5877.Birgbauer, E., Chun, J. N., New Developments in the Biological Functions of Lysophospholipids. Cell. Mol. Life Sci. 2006; 63:2695–2701Bittman, R., Perkins, W. R., Swenson, C. E. TLC ELL-2: Liposomal ET-18-OCH3. Drugs of the Future . 2001; 26:1052.Bourre, J. M. Dietary Omega-3 Fatty Acids and Psychiatry: Moods, Behavior, Stress, Depression, Dementia and Aging. J. Nutr. Health Aging . 2005; 9:31–38.Chada, J. S. Preparation of Crystalline L-alfa-glycerophosphorylcholine-cadmium Chloride Adduct from Commercial Egg Lecithin. Chem. Phys. Lipids . 1970; 4:104–108.Chen, S., Li, K. W. Mass Spectrometric Identification of Molecular Species of Phosphatidylcholine and Lysophosphatidylcholine Extracted from Shark Liver. J. Agric. Food Chem.
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