New comprehensive biochemistry vol 04 phospholipids

PHOSPHOLIPIDS New Comprehensive Biochemistry Volume General Editors A NEUBERGER London L.L.M van DEENEN Utrecht ELSEVIER BIOMEDICAL PRESS AMSTERDAM-NEWYORK-OXFORD Phospholipids Editors J.N HAWTHORNE and G.B ANSELL Nottingham and Birmingham 1982 ELSEVIER BIOMEDICAL PRESS AMSTERDAM NEW YORK*OXFORD Elsevier Biomedical Press, 1982 All rights reserved N o part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without the prior permission of the copyright owner ISBN for the series: 0444 80303 ISBN for the volume: 0444 80427-7 Published by: Elsevier Biomedical Press Molenwerf 1, P.O Box 1527 1000 BM Amsterdam, The Netherlands Sole distributors for the LI.S.A.and Canada: Elsevier Science Publishing Company Inc 52 Vanderbilt Avenue New York, NY 10017, U.S.A Library of Congress Cataloging in Publication Data Main entry under title: Phospholipids (New comprehensive biochemistry; v 4) Includes bibliographical references and index Phospholipids phospholipids-Metabolism I Hawthorne, J.N (John Nigel) 11 Ansell, G.B (Gordon Brian) 111 Series QD41S.N48 VOI.4 574.19'2s [574.19'214] 82-18382 [QP752.P53] ISBN 0-444-80427-7 (U.S.) Printed in The Netherlands To the memory of Maurice Gray (1930-1980), a good friend and dedicated lipid biochemist This Page Intentionally Left Blank Preface In the general preface to the original series of volumes entitled Comprehensive Biochemistry, Florkin and Stotz stated: “The Editors are keenly aware that the literature of biochemistry is already very large” Even so, the chemistry of the phospholipids formed only part of Vol (1965) and the whole of lipid metabolism was covered in Vol 18 published in 1970, of which only a small part was concerned with phospholipid metabolism For the present series, therefore, we were charged by the General Editors to produce a volume on phospholipids which was to emphasise metabolic aspects since their structural role in membranes was covered in Vol We had to ensure coverage of developments in the last decade while, at the same time, summarising essential findings of earlier periods There are various ways in which the book could have been organised As will be seen, we finally decided to devote separate chapters to individual or closely related phospholipids in which the essential chemistry is first described followed by an account of the metabolism, due regard being paid to the pioneering work of the past We have included a chapter on phospholipases in general and one on phospholipase A2 since its structure and the mechanism of its action have been investigated in greater detail than any other phospholipid metabolising enzyme The increasingly important topic of phospholipid exchange proteins is also treated separately Furthermore, since the use of biochemically defined mutants shows great promise for the better understanding of phospholipid biosynthesis and function, a chapter has been devoted to genetic control of the enzymes involved This book is intended for advanced students and research workers and we believe that it gives a comprehensive, though not exhaustive, account of phospholipid biochemistry, Throughout, the reader will discover how advances in techniques have added to our knowledge of the ever-expanding field Though it is difficult sometimes to avoid the impression that all research work is confined to the liver we hope that key references to other organs and other organisms will enable those whose interest lies outside the peritoneal cavity to be satisfied If the contents of the book belie the general title of the series, the responsibility lies with the editors not the authors and we would appreciate comments on errors and omissions We are grateful to Mrs J Paxton for her help in the preparation of the subject index J.N Hawthorne G.B Ansell Nottingham and Birmingham, August 1982 Contents Preface Chapter I Phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine, by G.B Ansell and S Spanner vii i 1 4 lntroduction Discovery and chemistry (a) Phosphatidylcholine and lysophosphatidylcholine (b) Phosphatidylethanolamine (c) Phosphatidylserine Determination and distribution in animal tissues Biosynthesis (a) Phosphatidylserine (i) Base-exchange (ii) Other reactions (b) Phosphatidylethanolamine (i) Decarboxylation of phosphatidylserine (ii) Cytidine pathway (iii) Base-exchange reaction (iv) Acylation of lysophosphatidylethanolamine (v) General comments on phosphatidylethanolamine synthesis (c) Phosphatidylcholine (i) Stepwise methylation (ii) Cytidine pathway (iii) Base-exchange (iv) Acylation of lysophosphatidylcholine (v) Transacylation of lysophosphatidylcholine (vi) Metabolism of phosphatidylcholine in the lung Catabolic pathways Aspects of sub-cellular metabolism Transport in the body (a) Absorption and the formation of chylomicrons (b) High-density lipoproteins (c) The liver and the production of phospholipids for bile and plasma (d) Metabolism in amniotic fluid The effects of drugs and other agents on metabolism (a) Some effects on biosynthesis (b) The modulation of methylation and decarboxylation by drugs and neurotransmitters (c) Phosphatidylcholine and acetylcholine synthesis in the brain (d) Roles of phosphatidylserine Conclusion References 7 9 12 12 12 13 14 14 16 17 17 18 20 23 28 28 29 29 33 33 34 34 39 40 41 41 Chapter Plasmalogens and 0-alkyl glycerophospholipids, by L.A Horrocks and M.Sharma 51 Introduction Nomenclature 51 51 Discovery and structure Methods and chemical properties 52 53 55 Chemical synthesis Content and composition (a) Bacteria (i) Phytanyl ethers (ii) Plasmalogens (b) Protozoa fungi, and plants (c) Invertebrates (d) Fish (e) Mammals and birds (i) Heart and skeletal muscle (ii) Nervous system (iii) Other organs (0 Neoplasms Biosynthetic pathways (a) Synthesis of long-chain alcohols (b) Synthesis of 0-alkyl bonds (c) Synthesis of plasmalogens Catabolic pathways Turnover of ether-linked glycerophospholipids 10 Platelet activation factor 11 Function and biological role References 56 56 56 58 60 60 61 62 63 63 68 71 72 72 73 75 79 81 81 83 85 Chapter Phosphonolipids, by T Hori and Y Nozawa 95 Historical introduction and classification Methods of isolation and characterization (a) Isolation and purification (b) Characterization (i) Infrared spectrometry of intact phospholipids (ii) Gas-liquid chromatography and mass spectrometry (iii) Nuclear magnetic resonance spectroscopy Occurrence and distribution (a) Qualitative and quantitative distribution of phosphonolipids (b) Fatty acid and sphingosine base compositions Metabolism (a) Biosynthesis (i) 2-Aminoethylphosphonic acid (AEPn) (ii) Glycerophosphonolipids (GPnL) (iii) Sphingophosphonolipids (SPnL) (b) Degradation Phosphonolipids and membranes of Tetrahymena (a) Intracellular distribution (b) Mechanism for enrichment of GPnL in the surface membranes (c) Roles in membrane lipid adaptation (i) Temperature (ii) Nutrition (iii) Alcohols (iv) Aging Other possible physiological functions References 95 97 97 98 98 98 99 99 99 103 107 107 107 107 111 111 112 112 115 115 I7 121 124 124 125 125 470 C.R.H Raetz trichloroacetic acid-precipitable phospholipid (Fig 7) at elevated temperatures, i.e 40°C [60] [Methyl-'4C]cholineis metabolized primarily to phosphatidylcholine and sphingomyelin by intact CHO cells, and other macromolecules are not labeled under these conditions [60] Consequently, viable cells immobilized on paper (rather than preparations made permeable) have been used in these experiments, permitting all steps of phosphatidylcholinesynthesis to be screened simultaneously [ 17,181 Mutant 58, identified by this approach, is specifically defective in phosphatidylcholine synthesis while several other isolates also obtained from the same screening are blocked in thymidine and leucine incorporation as well as choline metabolism [60] Further analysis of mutant 58 has revealed that the strain grows almost normally at 33"C, the permissive temperature, but divides only once or twice at 40°C, the restrictive temperature [60] After 20 h of incubation at 40"C, the phosphatidylcholine level declines from 41% to 21% in the mutant, while other phospholipids, including sphingomyelin, continue to be made [60,60a] Parental cells contain 50-58% phosphatidylcholineat both temperatures Ion-exchange chromatography of water-soluble choline metabolites isolated from mutant 58 reveals that the phosphocholine level is elevated about 3-fold, both at 33°C and at 40°C in the mutant, while CDP-choline decreases from 0.4 nmol/mg protein to less than 0.07 nmol/mg protein when the mutant is shifted to elevated temperatures [60,60a] Wild-type cells maintain the same CDP-choline level (0.5-0.6 nmol/mg protein) at both temperatures [60,60a] To confirm that mutant 58 is defective in the synthesis of CDP-choline, extracts have been prepared from mutant and wild-type cells A 40-fold reduction in the specific activity of the CDP-choline synthase is observed in mutant 58, and mixing experiments exclude the production of inhibitors of CDP-choline synthesis by the mutant [60,60a] Other enzymes of phosphatidylcholine synthesis are unaffected by this mutation Temperature-resistant revertants derived from mutant 58 regain nearly normal levels of CDP-choline synthase [60a] These studies provide the first genetic evidence that CDP-choline is the primary precursor of the phosphochofine head group of phosphatidylcholine in any mammalian system The availability of mutants of this kind provides new approaches to studies of the regulation of the membrane phosphatidylcholine content and creates the possibility of eventually isolating and mapping the genes involved in phosphatidylcholine metabolism by analogy to the gene cloning studies already in progress with E coli (see above) The continued synthesis of sphingomyelin under conditions of CDPcholine limitation [60] suggests that CDP-choline is not the direct precursor of sphingomyelin, but that a reaction involving lecithin as the donor of the phosphorylcholine head group is more likely [163,164] The observation that mutant 58 is temperature-sensitive for growth in the presence of 10%bovine fetal serum (which is a component of the growth medium) is especially intriguing This level of serum contributes approx 20-50 pM choline-linked phospholipids to the growth medium, particularly phosphatidylcholine Bnd lysophosphatidylcholine bound to lipoproteins (Esko, J.D and Raetz, C.R.H., unpublished) If receptor-mediated uptake of lipoproteins [ 165,165al could deliver Genetic control of phospholipid bilayer assembly 47 some of this material intact to the appropriate subcellular membranes, the temperature-sensitive phenotype of mutant 58 should be bypassed Since phenotypic suppression does not occur, it appears that CHO cells not possess adequate mechanisms for lipoprotein uptake, or alternatively that phospholipids incorporated during lipoprotein endocytosis are extensively degraded Mammalian lysosomes are known to contain a phospholipase C [ 1261, and all sub-cellular membranes have phospholipase A activity [ 1251 Because of the inadequacy of serum, it is of interest that phosphatidylcholine dispersions added to the growth medium effectively suppress the phenotype of mutant 58 at 40°C (Fig 8) Even colony formation from single cells is restored (data not shown) This finding suggests that there are mechanisms for the functional utilization of certain preparations of exogenous phospholipids during membrane biogenesis, and it demonstrates that the temperature-sensitive phenotype of mutant 58 can be attributed to the lesion in CDP-choline synthase [60,60a] and not some secondary mutation In addition to bovine liver and egg lecithin dispersions, phenotypic bypass can be achieved by chemically synthesized dipalmitoyl lecithin and by lysolecithin (Esko, J.D., Nishijima, M and Raetz, C.R.H., unpublished) Serum lipoproteins can be removed by KBr flotation [167] without affecting the ability of either lecithin or lysolecithin to correct the growth defect The lysolecithin bypass demonstrates that the acyltransferases specific for lysophospholipids, originally described by Lands [168,169], can be sufficient to support cellular growth, when de novo synthesis is blocked by mutation The chemically detected phosphatidylcholine content of mutant r + 40pM CONTROL LECITHIN PARENT CHO.KI PARENT CH0.K I I I? n \ v -110 ) -1 W V MUTANT CT"-58 shirt 20 40 60 HOURS I 80 I 100 120 20 40 60 80 100 120 HOURS Fig Growth of parental CHO'KI and mutant 58 cells at 40°C in the absence and presence of exogenous lecithin Multiple 60 mm dishes were inoculated with about lo5 cells and incubated at 33°C for 24 h Thereafter cultures were shifted to 40°C in the absence (left panel) or in the presence (right panel) of 40 pM egg lecithin, added from a concentrated sonic dispersion At indicated times cells from duplicate dishes were dispersed with trypsin [166] and counted on a Coulter Model B Counter The author thanks J.D Esko and M Nishijima for providing the above data 472 C.R.H Raetz 58 at 40°C is raised to about 80% of the wild-type level by the inclusion of lysolecithin in the medium (data not shown) The possibility of bypassing phospholipid synthesis de novo by exogenous supplementation in CHO cells will be especially useful for the isolation of additional mutants in this process, since the frequency of observed mutations may be much higher if synthesis de novo is rendered non-essential Conditionally lethal mutations are less frequent than lesions that cause an absolute defect independent of temperature The possibility of introducing exogenous phospholipids into CHO cells in a functionally useful state differs from similar attempts to correct lipid lesions in mutants of E coli [31] As noted above, McIntyre and Bell [31] supplemented mutants defective in glycerol-3-phosphate acyltransferase with lysophosphatidic acid and observed extensive binding, but phenotypic bypass could not be demonstrated The mechanisms by which exogenous lipids enter cells to cause phenotypic bypass also deserve further study Whether it is a simple fusion process [ 1701 or is mediated by specific proteins (or surface receptors) remains to be determined It is probable that the mechanisms for lysolecithin uptake will be different from those for lecithin incorporation While mutant cells are capable of increasing their chemical phosphatidylcholine content, by utilizing some fraction of the supplement, it appears that wild-type cells not this The inclusion of lecithin or lysolecithin in the growth medium of parental CHO cells does not alter their phosphatidylcholine content, suggesting that cells may regulate the net uptake of the exogenous lipid depending on their need for it (Esko, J.D., Nishijima, M and Raetz, C.R.H., in preparation) (c) Other assays in situ for detection of lipid enzymes in CHO colonies Mutant 58 was isolated by permitting intact cells to incorporate [methyl-'4C]choline in vivo [60] It is also possible to assay some of the mammalian phospholipid enzymes directly in situ by rendering the cells permeable and labeling with appropriate precursors in vitro [ 17,181 For instance, the CDP-ethanolamine and CDP-choline phosphotransferase reactions can be assessed in colonies, and a variant with an altered ethanolamine phosphotransferase has recently been obtained [71a] Excellent autoradiographic assays for the microsomal glycerol-3-phosphate acyltransferase, phosphatidylinositol synthase (CDP-diacylglycerol inositol phosphatidyltransferase, EC 2.7.8.1 1) [ 171 and phosphatidylglycerophosphate synthase have also been developed (Raetz, C.R.H., unpublished), but mutants are not yet available 15 Summary The identification by empirical methods of the genetic material coding for the phospholipid enzymes is beginning to provide a vast, new base of information on which to formulate hypotheses regarding membrane biogenesis and function Features of phospholipid structure which are essential or non-essential for growth are Generic control of phospholipid bilayer assembly 473 becoming clearer, and this has implications for the role of phospholipid asymmetry and phospholipid physical properties in biological systems While most of the genetic studies to date have provided physiological verification of the metabolic schemes derived from earlier enzymological investigations, many new biochemical findings have been uncovered by this work In E coli, the study of the dgk locus [7,8] has explained the function of the kinase in a diglyceride recycling system, and the studies of the dgkR regulatory mutants (Table5) have led to the inescapable conclusion that there are regulatory proteins (or metabolites) that help to determine the level of phospholipid gene expression The study of phosphatidylglycerol genetics has revealed two interacting genes, a structural gene ( pgsA) and a secondary gene ( pgsB) which may provide a link between phosphatidylglycerol and lipopolysaccharide formation [55,87] Two novel glycolipid species have been isolated in the course of this work, which have implications for the order of lipopolysaccharide assembly [ 171 Gene cloning 19- 12,129- 13I ] has been especially productive in bridging biochemical and genetic studies and can be expected to provide a wealth of additional structural information in the near future Cloning of the psd gene has revealed the existence of a soluble form of the decarboxylase, possibly an intermediate in maturation and membrane insertion [ 101 Mapping and cloning studies of plsB and dgk have revealed a very close linkage of these two phospholipid genes, necessitating a search for common regulatory elements The perturbation of the antibiotic resistance spectrum of E coli cells harboring either the pss [85] or the cds [56,56a] mutations may prove useful for the design of new drugs and the treatment of gram-negative infections Studies with inositol and choline auxotrophs of lower eukaryotes [ 19,211 have suggested the existence of precise mechanisms for the control of the phospholipid content and the polar headgroup charge Most exciting is the feasibility of extending phospholipid genetics to complicated, higher eukaryotic systems [ 17,18,60,7I] The characterization of CDP-choline synthase mutants [60] suggests that there are mechanisms for phospholipid uptake which can support cellular growth and which are enhanced by phospholipid depletion due to mutation Work in higher eukaryotic systems is only beginning and should be complemented by similar studies of lower eukaryotic organisms such as S cereuisiae Fundamental mechanisms for the regulation of membrane biogenesis are certain to emerge Acknowledgements I am indebted to Jeffrey Esko, Barry Ganong and William Dowhan for their critical reading of the preliminary version of this manuscript I thank Sarah Green for her assistance and patience during the preparation of this article This work was supported in part by United States Public Health Service grants AM 21722, AM 19551 and 1K04-AM00584 474 C.R.H Raetz References Raetz, C.R.H (1978) Microbiol Rev 42, 614-659 Cronan Jr., J.E (1978) Annu Rev Biochem 47, 163-189 Bell, R.M and Coleman, R.E (1980) Annu Rev Biochem 49, 459-487 3a Bell R.M., Ballas, L.M and Coleman, R.A (1981) , J Lieid Res 22, 391-403 Van den Bosch, H (1974) Annu Rev Biochem 43, 243-277 Bloch K and Vance, D (1977) Annu Rev Biochem 46, 263-298 Snyder, F (Ed.) 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phosphatidylethanolamine 35 Adrenccorticotrophic hormone, and triphosphoinositide 275 Aldehydohydrolase 80 Alk- 1-enyl hydrolase 80 0-Alkyl bonds, biosynthesis 73 1-Alkyl-2-acetyl-GPC acetylhydrolase 83 Alkylacyl-GPC, preparation of 53 Alkylacylglycerophosphate, chemical synthesis 55 Alkylacyl glycerophospholipids, chemical syn thesis 55 Alkyldihydroxyacetone phosphate 73 Alkylglycerol monooxygenase 80 Alkylglycerols assay of 54 chemical synthesis 55 in marine invertebrates 62 peroxidation of 55 Alkyl lysophospholipids, phospholipase D, hydrolysis of 346 1-Alkyl-sn-glycero-3-phosphate 73, 79 Aminoethylphosphonic acid, biosynthesis 107 Aminoethylphosphonic acids 95 Amniotic fluid, phosphatidylcholine of 33 phosphatidylglycerol of 247 Animal cell colonies, mutant isolation from 442 Arachidonate, phospholipid source of, in prostaglandin production 336 Arginine, in phospholipase A, 396 Asymmetry, of membranes and transfer proteins 30 of membrane phospholipids 23 Base-exchange, and phosphatidylserine biosynthesis for phosphatidylcholine biosynthesis 16 for phosphatidylethanolamine biosynthesis 12 Batyl alcohol 52 Behenic acid 130 Benfluorex 202 Bile phospholipids 19 Bis(diacy1glycero)phosphate I7 Bis(monoacylglycero)phosphate,biosynthesis 235 degradation 240 drug-induced lipidoses 25 I in lipid storage diseases 250 storage mechanism 252 structure 216 subcellular localisation 246 synthetase 236 Bis-phosphatidic acid 21 Carboxylate groups, in phospholipase A, 395 Cardiolipin, and E coli cell growth 445 structure 216 Cardiolipin synthase mutants 458 Carnitine acyltransferase 188, 189 CDP-choline 15 CDP-choline synthase, isolation of animal cell mutants lacking 444 CDP-diacylglycerol 269 CDP-diacylglycerol hydrolase 454 CDP-diacylglycerol-inositol 3-phosphatidyltransferase 180 CDP-diacylglycerol 3-phosphatidyltransferase 269 CDP-diacylglycerol synthase mutants 452 CDP-diacylglycerol, synthesis from phosphatidate 192 CDP-ethanolamine 1 Ceramide 130 Ceramide aminoethylphosphonate 95 Ceramide, chemical synthesis 131 Chimyl alcohol 52, 97, 121 Cholesteryl-ester exchange protein 286 Choline auxotrophs 442, 464 of yeasts 466 Choline, discovery Choline kinase 10, 14 Choline oxidase 348 Choline phosphotransferase, in outer leaflet of e.r 26 480 Choline plasmalogen, in neoplasms of spermatozoa 69 neuronal turnover of 77 Chylomicrons and phosphatidylcholine 28 Ciliatine 95 Cilienic acid 114, 117 Clofenapate 183, 191 Clofibrate 191 and fatty acid oxidation 190 CMP-aminoethylphosphonate 107 Cytidine auxotrophs 454 Diabetic neuropathy, and inositol 276 Diacylglycerol acyltransferase 180 in diabetes 205 Diacylglycerol kinase 180, 184 mutants, 451 Diacylglycerol lipase, in platelets 337 Diethylaminoethoxyhexestrol,lipidosis, 25 Dihydrosphingosine 130 Dihydroxyacetone phosphate acyltransferase 180, 183 peroxisomal 184 Dihydroxyacetone phosphate, esterification 183 Dipalmitoyl-phosphatidylcholine 18 Diphosphatidyl(glucosyl)glycerol226 Diphosphatidylglycerol, biosynthesis 232 chemical synthesis 218 phospholipase A hydrolysis 239 phospholipase D hydrolysis 239 structure 216 subcellular localisation 244 Diphosphatidylglycerol synthetase 235 Diphosphoinositide 265 Diphosphoinositides, of yeast 466 Endoplasmic reticulum and phospholipid synthesis 24 Erythrocyte, exchange of phospholipid with serum 32 phospholipid pattern in various mammals 157 Escherichia coli, location of phospholipid mutants 447 Escherichia coli mutants, isolation of 436 Escherichia coli, phospholipid pathways 446 Ethanol, and triacylglycerol synthesis 190 Ethanolamine kinase 10 Ethanolamine phosphotransferase, isolation of animal cell mutants lacking 444 Ethanolamine plasmalogen 52 methylation in brain 77 of brain 63 of myelin 63 Ethanolamine plasmalogens, in microsomes and synaptosomes of nerve tissue 65 in nervous tissue 65 nervous tissue, aryl and alkenyl composition 67 Ether-linked lipids, catabolism 79 of neoplasms of spermatozoa 69, 70 turnover 81 Ether-linked phospholipids, in heart and skeletal muscle 64 Ether lipids, discovery 52 in birds 62 in mammals 62 of fish 61 of fungi 60 of invertebrates 60 of plants 60 of protozoa 60 Fatty acid synthesis, coupling to phospholipid synthesis in E coli 450 Fructose, and triacylglycerol synthesis 190 Glucagon, and fatty acid metabolism 188 Glucocorticoids, and fatty acid metabolism 188 and phosphatidate phosphohydrolase 201 and phospholipase A, inhibition 326 Glucosaminylphosphatidylglycerol219, 226 Glucose, and triacylglycerol synthesis 190 sn-Glycero-1-phospholipids58 Glycero-3-phosphate dehydrogenase 180 Glycero-3-phosphate dehydrogenase (NAD+ ) 180 Glycerol plasmalogen 59 Glycerol-3-phosphate acyltransferase, mutants 447 Glycerol-3-phosphate, and phosphatidate biosynthesis 179 Glycerol-3-phosphate auxotrophs 447 Glycerol-3-phosphate dehydrogenase mutants 45 Glycerophosphate acyltransferase 180 fatty acid specificity 182 microsomal 182 mitochondria1 182 subcellular localization 181 Glycerophosphate dehydrogenase (NAD+ ) 186 Glycerophosphate phosphatidyltransferase 180, 456 Glycerophosphoethanolamines,alkylacyl in nerve tissue 66 Glycerophosphoglycerol2 17 48 Glycerophosphonolipids 96, 16 Glycerophosphonolipid, of Tetrahymena fatty acid composition and growth temperature 118 Halofenate 191 High-density lipoproteins 29 Histidine, in phospholipase A, 390 Hydroxysphinganine 130 , Indomethacin, inhibition of phospholipase A 336 Inositol auxotrophs 442,464 in yeasts 465 isolation 444 of CHO cells 468 Inositol 1,2-cyclic phosphate 270 Inositol phosphatidyltransferase, in livers of diabetic rats 194 Insulin, and fatty acid metabolism 188 Lecithin Lecithin-cholesterol acyltransferase 29 Lignoceric acid 130 Lipid storage diseases 250 Lipidoses drug-induced 25 inherited 250 Lipolysis, mechanisms of, with phospholipase A 369 Liposomes, therapy with 41 Long-chain alcohols, biosynthesis 72 Low-density lipoprotein 29 Lung, phosphatidylcholine of 18 Lung surfactant 33 phosphatidylglycerol of 247 Lysine, in phospholipase A,, 394 Lysophosphatidate 181 Lysobisphosphatidic acid, structure 216 Lysolecithin acyltransferase 17 Lysophosphatidylcholine 17 acylation of 17 discovery, chemistry intestinal absorption 28 of plasma 32 tissue levels transacylation 333 Lysophosphatidylethanolamine, acylation 12 Lysophosphatidylglycerol226, 316 Lysophospholipase 17,327 assay 327 Lysophospholipase A 79 346 Lysophospholipases, Occurrence 327 Lysophospholipase, properties 328 purification 33 I subcellular distribution 327 Mast cell, and phosphatidylserine 36 Membrane asymmetry, and sphingomyelin 16 transfer protein studies of 301 Membrane biogenesis and transfer proteins 305 Methionine, in phospholipase A, 393 Monoacyl-glycerophosphate acyltransferase 180 181 Monoacyl glycerophosphate, esterification 18 I Monolayers, and transfer proteins 293 Myo-inositol 263 Neoplasms, ether-linked lipids of 71 Nervonic acid 130 Niemann-Pick disease 134,250 types of 136 Nitrophenylacetate 332 1-0ctadecyl-2-acetyl-sn-glycero-3-phosphocholine 81 Oestradiol- 17/3 and lung phospholipids 34 , Palmitoyl cellulose, chromatography 18 Palmitoyl-propane- I-phosphocholine 330 Palmitoyltransferase 83 Paramecium, aging and phospholipids 124 Peroxisomes, lipid metabolism of 191 Phase transitions, of membranes and ether lipids 89 Phenobarbital, and liver triacylglycerol synthesis 191 Phosphatidate, biosynthesis from acylglycerols 184 biosynthesis from dihydroxyacetone phosphate 183 biosynthesis from glycerophosphate 179 control of synthesis 187 conversion to diacylglycerol 194 Phosphatidate cytidylyltransferase 180, 192 Phosphatidate, deacylation of 197 effect of cationic drugs on metabolism 198 Phosphatidate phosphohydrolase 180, 194 and triacylglycerol synthesis 201 soluble, and lipolytic agents 206 soluble and microsomal 196 subcellular distribution 195 Phosphatidate, synthesis from glycerophosphate and dihydroxyacetone phosphate compared 185 Phosphatidic acid, plasmalogen 68 transfer protein 292 482 Phosphatidylcholine, and brain acetylcholine 39 biosynthesis 13 CHO mutants 468 discovery, chemistry in lung 18 intestinal absorption 28 molecular species in rat tissues tissue levels Phosphatidylethanolamine,biosynthesis discovery, chemistry Phosphatidylethanolamine methylation 14 asymmetry 26 Phosphatidylethanolamine, methylation in choline auxotrophs 464 methylation in mast cells 36 molecular species in animal tissues tissue levels Phosphatidylglycerol, biosynthesis 228 Phosphatidylglycerol condensation pathway, in bacteria 234 Phosphatidylglycerol, degradation 238 diether form 56 formation by transphosphatidylation using phospholipase D 347 hydrolysis by phospholipases 19 in amniotic fluid 249 in CHO cells lacking inositol 468 source of diacylglycerol in E coli 452 structure 216 subcellular localization 241 Phosphatidylglycerolsulphate,diether form 56 Phosphatidylglycerol turnover in E coli 458 Phosphatidylglycerophosphatase23 Phosphatidylglycerophosphate,biosynthesis 229 diether form 56 Phosphatidylglycerophosphatesynthase, mutants 456 Phosphatidylglycerophosphatesynthetase 23 Phosphatidylinositol 263 and calcium-gating 273 biosynthesis 268 catabolism 270 fatty acid composition 193 Phosphatidylinositol mannosides 265 biosynthesis 270 Phosphatidylinositol, of yeast 466 Phosphatidylinositol phosphodiesterase 270 Phosphatidylinositol, plasmalogen 68 Phosphatidylinositol4.5-bisphosphate 265 biosynthesis 269 Phosphatidylinositol4-phosphate265 biosynthesis 269 Phosphatidylserine, and histamine release from mast cells 36 and opiates 40 biosynthesis Phosphatidylserine decarboxylase mutants 56 Phosphatidylserine, discovery, chemistry formation by transphosphatidylation using phospholipase D 347 molecular species in rabbit muscle mutants 455 Phosphatidylserine synthase, bacterial purification 461 Phosphatidylserine, tissue levels Phosphoinositides, chemistry, 263 discovery 263 distribution 267 fatty acids of 268 Phospholipases A, and reacylation 335 Phospholipase A , , and lipase 16 detergents and specificity 317 occurrence, assay 14 properties 316 purification 316 Phospholipase A,, amino acid sequence 363 and prostaglandins 335 assay 320, 360 binding of substrate analogues 407 binding to aggregated lipids 409 calcium binding 404 calcium ion activation 324 chemical modification 389 catalytic mechanism 421 3-dimensional structure 415 immunology 414 kinetics, with bilayer substrates 379 with micellar substrates 371 with monolayers 377 with monomeric substrates 369 occurrence 320 polymeric or monomeric 387 properties 32 purification 321, 360 regulatory proteins 325 reversible inhibition of 387 specific for phosphatidate 198 structure 363 X-ray analysis 415 zymogen-type regulation 324 Phospholipase B 314 of P notaturn 18 Phospholipases C, assay 337 483 Phospholipase C, classification 338 degradation of ceramide aminoethylphosphonate 112 hydrolysing phosphatidylinositol270 hydrolysis of cardiolipin 218 lysosomal 334 Phospholipases C, occurrence 337 Phospholipase C, properties 340 purification 340 release of arachidonate from PI in platelets 337 specificity 339 Zn2+ activation 341, 343 Phospholipase D, and base-exchange 345 assay 344 occurrence 344 properties 348 purification 348 specific for cardiolipin 345 Phospholipases, nomenclature 13 Phospholipid exchange proteins 279 Phospholipid, patterns of erythrocytes of various mammals 157 Phospholipid perturbations, and E coli cell growth 445 Phospholipid transfer proteins, determination of activity 280 discovery 279 distribution 281 Phospholipid turnover 334 Phospholipidosis, due to hydrophobic cationic drugs 199 Phosphonic acids 95 Phosphonoacetaldehyde hydrolase I Phosphonatase 11 Phosphonoenolpyruvate 107 Phosphonolecithin 110 Phosphonolipids, biosynthesis 107 characterizaton 98 classification 95 degradation of 11 distribution 99 fatty acids of 103 history 95 intracellular distribution in Terruhymena 12 isolation 97 sphingosine bases of 104 Phytanyl ether lipids structures 57 Phytanyl ethers, of bacteria 56 Phytanyl groups, biosynthesis 58 Phytoglycolipid 266 Phytosphingosine 130 Plasma lipoproteins, lipid composition 160 Plasmalogenase 80 Plasmalogens, assay of 53 biosynthesis 75 discovery 53 hydrolysis of 54 in birds 62 in cultured cells 72 in human tissues 64 in mammals 62 in marine invertebrates 62 of bacteria 58 of heart and skeletal muscle 63 preparation of 53 Platelet-activating factor 81 Polyglycerophosphatides,distribution 221 fatty acids of 226 Polyglycerophosphatide synthesis, mutants 456 Polyglycerophospholipid, content in animal tissues 222 content in microorganisms 224 content in plant tissues 223 Polyglycerophospholipidsdiscovery 16 Polyphosphoinositides, catabolism 27 Prostaglandin precursors, and phospholipase A 335 Protein phosphorylation, and polyphosphoinositides 275 Pulmonary surfactant 33 phosphatidylglycerol of 247 Red blood cell, exchange of phospholipid with serum 32 Respiratory distress syndrome 247 Selachyl alcohol 1, 52 Semilysobisphosphatidic acid 217 serine base-exchange enzyme 346 serine, in phospholipase A, 390 spermatozoa, ether-linked lipids of 69 Sphinganine 130 Sphingenine 130 Sphingolipids, containing inositol 266 Sphingomyelin 133 and acetylcholinesterase 156 and aging 161 biosynthesis 133 and membrane integrity 164 and membrane permeability 165 and membrane viscosity 165 chemical synthesis 130 composition 129 484 in aging human eye lens 163 in atherosclerosis 161 in cataract 163 in membrane asymmetry 161 in plasma lipoproteins 158 interaction with bile salts 155 interaction with cholesterol 151 interaction with phosphatidylcholine 150 interaction with proteins 155 interaction with Triton X-100 153 liposomes of 139 molecular models 146 molecular motion in bilayers 149 monolayers of 140 sphingomyelin, of sheep erythrocyte 155 physical properties 137 tissue distribution 159 thermotropic behaviour 141 Sphingomyelinase 134 Sphingomyelin, enzymatic hydrolysis 134 Sphingomyelinase, assay 135 purification 134 Sphingophosphonoglycolipids 96 distribution '102 Sphingophosphonolipids 96 biosynthesis 111 distribution 103 sphingosine bases of 108 Sphingosine 130 Sphingosine-I-phosphate, release of phosphoethanolamine from 10 Sphingosine, phosphorylation 10 Sulphydryl goups, in phospholipase A, 390 Tetrahymanol 112 Transbilayer, movement of phospholipids 301 Transfer protein, and membrane biogenesis 305 binding studies 293 causing membrane asymmetry 305 control of activity by membranes 298 for phosphatidic acid 292 hydrophobic and electrostatic interactions with phospholipids 294 immunological aspects 292 membrane specificity 292 mode of action 292 net phospholipid transfer 296 non-specific 284 of brain 284 of heart 284 of liver 284 of plants and microorganisms 286 phosphatidylcholine 284 phosphatidylinositol284 phospholipid specificity 29 physiological role 304 properties 287 purification 284 Transphosphatidylation, and phospholipase D 345 by phospholipase D 347 Triphosphoinositide 265 of yeast 466 Tryptophan, in phospholipase A, 392 Tuberculostearic acid 268 Tyrosine, in phospholipase A 398 .. .PHOSPHOLIPIDS New Comprehensive Biochemistry Volume General Editors A NEUBERGER London L.L.M van DEENEN Utrecht ELSEVIER BIOMEDICAL PRESS AMSTERDAM-NEWYORK-OXFORD Phospholipids. .. Company Inc 52 Vanderbilt Avenue New York, NY 10017, U.S.A Library of Congress Cataloging in Publication Data Main entry under title: Phospholipids (New comprehensive biochemistry; v 4) Includes bibliographical... entitled Comprehensive Biochemistry, Florkin and Stotz stated: “The Editors are keenly aware that the literature of biochemistry is already very large” Even so, the chemistry of the phospholipids