New comprehensive biochemistry vol 14 plasma lipoproteins

VII Acknowledgement I wish to acknowledge the outstanding editorial assistance of Mrs Beth Flinn in the preparation of this book, and to thank Dr Henry Pownall for his helpful comments 1987, Elsevier Science Publishers B.V (Biomedical Division) All rights reserved No 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 written permission of the publisher, Elsevier Science Publishers B.V (Biomedical Division), P.O Box 1527, 1000 BM Amsterdam (The Netherlands) Special regulation for readers in the U.S.A.: This publication has been registered with the Copyright Clearance Center Inc (CCC), Salem, Massachusetts Information can be obtained from the CCC about conditions under which the photocopying of parts of this publication may be made in the U.S.A All other copyright questions, including photocopying outside of the U.S.A., should be referred to the publisher lSBN for the series: 0-444-80303-3 ISBN for the volume: 0-444-80855-8 Published by: Elsevier Science Publishers B.V (Biomedical Division) P.O Box 211 1000 AE Amsterdam (The Netherlands) Sole distributors for the U.S.A and Canada: Elsevier Science Publishing Company, Inc 52 Vanderbilt Avenue New York, NY 10017 (U.S.A.) Library of Congress CataloginginPublication Data Plasma l i p o p r o t e i n s (New comprehensive b io c h e m i s tr y ; v 14) I n c l u d e s b i b l i o g r a p h i e s and index Blood l i p o p r o t e i n s Blood l i p o p r o t e i n s - Metabolism I Gotto, Antonio M 11 S e r i e s [DNLM: Lipoproteins blood Lipoproteins-metabolism W NE372F v.14 / QU P7151 D415.N48 v o l 14 574.19'2 s [574.19'296] 87-13519 QPS3.3L521 ISBN 0-444-80855-8 (U.S.) Printed in The Netherlands Plasma Lipoproteins Editor A.M GOTTO, Jr Department of Medicine, Baylor College of Medicine, 6335 Fannin, M.S A-601, Houston, TX 77030, USA 1987 ELSEVIER Amsterdam - New York Oxford New Comprehensive Biochemistry Volume 14 General Editors A NEUBERGER London L.L.M van DEENEN Utrecht ELSEVIER Amsterdam New York - - Oxford V Preface In an earlier volume of New Comprehensive Biochemistry, Dr Paul Miller and I contributed a chapter on the current status of the metabolism of the plasma lipoproteins [l] In this rapidly evolving field of research, an enormous amount of new knowledge and understanding of lipoprotein structure, function and metabolism has emerged Since the last volume was published, Michael S Brown and Joseph L Goldstein received the Nobel Prize in medicine and physiology in 1985 for their pioneering work on the LDL receptor Their fundamental investigations have had a great impact not only on lipoprotein metabolism but on other areas of biology and medicine as well Their work on the LDL receptor helped clarify several aspects of lipoprotein metabolism as they relate to LDL Recently, the complete structure of apoB-100, the apolipoprotein of LDL, has been elucidated The determination of the structure of this protein had been the subject of intensive study for many years in various laboratories, but until recently, relatively little progress had been made The application of methods of molecular biology enabled the determination of the structure of cDNA to be determined and a great deal of the protein structure has been completed as well This work is reviewed in detail in the present volume by Yang and Chan The volume begins with chapters on structure, then proceeds to analyses of lipid and lipoprotein dynamics, metabolism, function, genetics, and molecular biology Doctor Breslow covers the subject of lipoprotein genetics in molecular biology in his review in the present volume; Dr Nestel discusses overall regulation and metabolism of the plasma lipoproteins; Drs Gianturco and Bradley, the role of lipoprotein receptors; and Dr Fogelman, the role of cellular regulation of cholesterol metabolism The chapter by Dr Patsch describes the latest developments and views on the metabolism of HDL The metabolism of the plasma lipoproteins is dependent on their structure and on the activities of various enzymes; the former being covered by Drs Pownall, Sparrow, Massey and Small, and the latter by Drs Tall, Jonas and Schotz in this volume Doctors Morrisett and Guyton review Lp(a), a topic that has been underrepresented in volumes on lipoproteins, but one that has begun attracting the attention of more investigators We expect that this volume would be mainly of interest to researchers who are interested in lipid and lipoprotein structure and metabolism The subjects covered are technical and biochemical in places but have great implications for clinical medicine and biology in general Antonio M Gotto, Jr VI References Miller, J.P and Gotto, A.M., Jr (1982) The plasma lipoproteins: their formation and metabolism in: Comprehensive Biochemistry (edited by A Neuberger and L.M van Deenen), Vol 19B, Part 11 Elsevier Scientific Publ Co., Amsterdam, pp 419-506, 1982 A M Gotto, J r (Ed.) Plasma Lipoproreins C 1987 Elsevier Science Publirhers B.V (Biomedical Division) CHAPTER I Structure of triglyceride-rich lipoproteins: an analysis of core and surface phases KURT W MILLER* and DONALD M SMALL Biophysics Institute, Departments of Biochemistry and Medicine, Housman Medical Research Center, Boston University School of Medicine, Boston M A 02118, USA I Introduction Intestinal chylomicrons and hepatic very low density lipoproteins (VLDL) serve as the major transport vehicles of triglyceride within the circulation These lipoproteins are collectively designated the ‘triglyceride-rich’ lipoproteins since under normal conditions of diet and time of residence in the plasma triglyceride is their major component Mammalian chylomicrons typically consist of - 2% protein and 98 - 99% lipid, of which 90% is triglyceride, 1-2070 cholesterol ester, 1% cholesterol, and - 8% phospholipid** VLDL contain appreciably more protein, - - 10070, and of their lipids, 65% is triglyceride, 12% cholesterol ester, % cholesterol, and 18% phospholipid Since they consist predominantly of lipid, chylomicrons and VLDL have buoyant densities less than plasma and can be isolated from other blood components by centrifugation VLDL and chylomicron size and density distributions overlap, and thus, to obtain VLDL largely of hepatic origin, patients or animals must be fasted for sufficient time to allow dietary chylomicrons t o be cleared from their plasma VLDL obtained from fasted individuals range in diameters from 350 - 750 If intestinal lymph VLDL are included in the category of intestinal chylomicrons, the range of lymph chylomicron particle sizes measured prior to their entry into the bloodstream range from 350 to > 000 A , with a diameter of 200 A being an average value after the ingestion of a meal containing fat Since the content of triglyceride-rich lipoprotein lipids greatly exceeds that of the apoproteins, a reasonable working hypothesis is that the arrangement of the lipids is key t o governing the overall structure of the lipoproteins The lipids are held A * Present address: Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, M D 20814, USA ** Unless otherwise indicated, all composition data are presented in weight percent units together solely by noncovalent forces, and are organized to lessen the unfavorable free energy of contact between hydrophobic lipid moieties and the surrounding water in which they are suspended Apoproteins are bound to the surface of the lipoproteins, and participate in stabilizing the lipid-water interface Since most of the apoproteins have several domains of amphiphilic a! helices [l], the hydrophobic part of the helix may form part of the surface by either directly acting with the core surface and essentially displacing surface phospholipid, or by adsorbing to surface lipids From this surface position in the particle, certain exposed hydrophilic regions may act as receptor ligands (apolipoprotein (apo)B, apoE), or serve as cofactors (apoCII, for lipoprotein lipase, the enzyme responsible for the cleavage of chylomicron and VLDL triglyceride) Certainly the structure of the lipid domains at the surface of the lipoprotein influences the binding conformation and catalytic properties of apoproteins and enzymes which adsorb t o its surface Since the compositions of the lipid and apoprotein components change in some cases dramatically during metabolism of the lipoprotein particle, it becomes important to determine how lipid and protein compositional changes are interrelated We will attempt to summarize what is presently known about the structural organization of chylomicron and VLDL lipids Since the arrangement of lipids within these lipoproteins is analogous to that of simple emulsion particles, it will be useful to discuss the properties of emulsion systems to acquire insight into the properties of the more complex lipoproteins After summarizing features of their structural organization, it will be possible to look in greater detail at their metabolism and address areas such as mechanisms of lipoprotein assembly, hydrolysis of triglyceride by lipoprotein lipase and formation of remnants, transfer of cholesterol ester and triglyceride between lipoproteins, and transfer of cholesterol into nascent triglyceride-rich lipoproteins after they enter the circulation Thus, one of the goals of this review is to discuss the compositional and structural changes which take place during the metabolism of chylomicrons and VLDL Chylomicron and VLDL metabolism The metabolism of triglyceride-rich lipoproteins has been extensively reviewed in the recent literature The reader is referred to reviews of lipoprotein and apolipoprotein synthesis and metabolism [2 - 141, action of lipoprotein lipase [ 15 - 181, and related areas such as fat absorption [19- 211 and lipid metabolism [22, 231 We will discuss the metabolism of chylomicrons and VLDL in parallel since many steps of their synthesis and transformation occur by common pathways Where possible, we will try to indicate how a thorough description of triglyceride-rich lipoprotein particle structure would facilitate the interpretation of metabolic data (a) Synthesis of nascent chylomicrons and VLDL The synthesis of triglyceride-rich lipoproteins occurs within the intracellular membrane compartments of intestinal enterocytes and liver hepatocytes The fatty acid and 2-monoacylglycerol precursors of chylomicron triglycerides are taken up by the enterocyte after being transported to the cells in bile salt micelles [19, 20, 241 Apparently, the monoglycerides subsequently are re-esterified to triglycerides and therefore most of the synthesis of triglyceride occurs independently of the glyceraldehyde 3-phosphate pathway, the predominant pathway for synthesis of triglyceride in the liver [22].Since little or no de novo synthesis of fatty acids occurs during the absorption of fat, the fatty acid profile of the chylomicron triglycerides closely resembles that of the dietary fat [25,261 Thus, chylomicron triglycerides have relatively high melting points if derived from ingested cream or butter fat or have low melting points if derived from most vegetable oils, such as corn or safflower oil [26, 271 The fatty acid composition of chylomicron phospholipids is relatively independent of that of the dietary fat [26,281, and a high percentage of the phospholipid species has saturated fatty acids at the sn-1 position and polyunsaturated fatty acids at the sn-2position of the glycerol backbone A small percent of the dietary cholesterol is in the form of cholesterol esters and must be hydrolyzed before absorption [21].Within the enterocyte a fraction of the cholesterol is esterified to fatty acids by acyl CoA:cholesterol acyltransferase (ACAT) to reform cholesterol esters [29- 321 Cholesteryl oleate and cholesteryl linoleate are common species of cholesterol esters found in nascent chylomicrons and VLDL The fatty acids which are incorporated into VLDL lipids in the hepatocyte are derived from multiple sources, namely de novo synthesis from acetyl-CoA units produced by carbohydrate utilization, free fatty acids taken up into the cells from plasma albumin, and from the hydrolysis of lipids transported to the liver in plasma lipoprotein such as chylomicron remnants [33 - 391 Furthermore, cholesterol can be supplied by de novo synthesis, or by uptake from the plasma [40].Most, if not all, of the synthetic machinery for triglyceride-rich lipoprotein lipid synthesis is present on the cytoplasmic side of the endoplasmic reticulum (ER) membranes [23] The synthesized lipids are then segregated into the lumenal aspects of the ER during the remainder of their transit through the cell It is clear that the cholesterol content of newly secreted, or nascent, chylomicrons and VLDL is significantly less than that of their plasma counterparts [41].The difference probably arises simply because the sites of nascent lipoprotein assembly are located at the minimum of a cholesterol concentration gradient which is lowest in the intracellular membranes [42],and highest in the circulatory system However, the level of intracellular cholesterol in the hepatocyte can be increased by prolonged feeding of cholesterol, and under these conditions, nascent VLDL become relatively enriched in their cholesterol contents [43 - 451 The composition of apoproteins in chylomicrons and nascent hepatic VLDL are similar Both contain apoB, a high molecular weight, extremely hydrophobic glycoprotein which contributes 10 - 30% to the total chylomicron and VLDL apoprotein mass in mammalian species [ l l , 461, and up to 50% in avian species [47, 481 Intestinal cells secrete only the small apoB of about 250 000 daltons, while hepatocytes produce large apoB which has a molecular weight of 350 000 - 400 000 [49] Also present on lymph chylomicrons (nascent triglyceride-rich particles)* are apoAI ( M , -28 000), the major apoprotein of plasma HDL, and apoC peptides (Mr - 12 000) of which apoCII ( M r 500) serves as the cofactor for lipoprotein lipase [50].Many of the apoC peptides present on lymph chylomicrons probably have been acquired by the chylomicrons upon their entry into the lymph [ l l , 511 The intestine secretes significant amounts of de novo synthesized apoAI and apoAIV (Mr 46 000) on chylomicrons [52] However, it does not secrete significant levels of chylomicron-associated apoE (Mr 32 - 35 000) In contrast, a small amount of apoE is probably secreted on nascent hepatic VLDL [53] As will be discussed below, the percentages of specific apoproteins bound to the lipoproteins change dramatically after nascent particles first enter the circulation, and then change continuously during their time of residence in the circulation The secretion of lipoprotein lipids is contingent upon the synthesis and secretion of apoproteins, as demonstrated by studies which show a complete block of lipid secretion after administration of cycloheximide, an inhibitor of protein synthesis [54] Study of patients with the disease abetalipoproteinemia has documented the importance of apoB synthesis and secretion in the process of chylomicron and VLDL production [6, 55, 561 These patients have no chylomicron or VLDL particles in their plasma, and also lack LDL, the metabolic end-product of catabolized VLDL Thus, their plasma triglyceride levels are extremely low, and not rise after the ingestion of a fatty meal Rather, the digested fat is esterified to triglyceride within their enterocytes and accumulates in intracellular fat droplets Apparently the secretion of HDL apoproteins is not markedly affected by the block in chylomicron and VLDL secretion, since plasma apoAI and apoC levels are fairly normal Since intracellular apoB cannot be detected in enterocytes by immunological procedures [57], it seems possible that a highly truncated and immunologically unrecognizable apoB molecule, or no apoB at all, is synthesized by these patients In another genetic abetalipoproteinemia, the synthesis of hepatic apoB is impaired while that of intestinal apoB is normal [56] These patients can absorb and transport dietary fat but cannot produce hepatic VLDL Early studies of hepatocytes in the process of VLDL synthesis suggest that apoB a ~ , dpresumably other apoproteins are combined with VLDL lipids, synthesized in the smooth ER, at or near specialized elements of the rough ER which have smooth* We will use ‘nascent triglyceride-rich particles’ to mean particles which have been secreted and collected from intestinal lymph or hepatic perfusion in the absence of blood cells or plasma These particles are not truly nascent as they have been exposed to intestinal lymph or hepatic perfusion fluid rupts the normal coding region of the apoA-I gene at approximately the codonspecifying residue 80 of the mature protein and may explain the lack of apoA-I in the plasma of these patients To define the nature of the DNA insertion, a genomic library was made from the DNA of one of the probands, and clones containing the apoA-I gene and the contiguous up and downstream portions of the insertion were isolated Southern blotting of genomic DNA from normal individuals, after digestion with EcoRI, with a probe that included apoA-I sequences and insertion sequences, revealed the normal 13 kb apoA-I genomic fragment, as expected, plus another unique band In the probands the same probe revealed only the 6.5 kb band This suggested that in the probands a unique piece of DNA, normally present in the genome, has been deleted and was inserted into the apoA-I gene Further experiments with a probe made to just the insert showed that it hybridized to a region ’ to the apoA-I gene in normal individuals, which contains the apoCIII gene [187] Thus, it appears that a portion of the apoCIII gene was inserted into the apoA-I gene in the probands and that this is the underlying molecular basis of their apoAI/apoCIII deficiency A ckn owledgernents This work was supported by grants from the National Institutes of Health (HL33714, HL32435, AG04727) Dr Jan L Breslow is an Established Investigator of the American Heart Association I would like to express my sincere appreciation to Miss Lorraine Duda for her expert assistance in preparing this review References Zannis, V.I and Breslow, J.L (1985) Adv Hum Genet 14, 125-215 Herbert, P.N., Assmann, G., Gotto, A.M., Jr and Fredrickson, D.S (1982) in: The Metabolic Basis of Inherited Disease (J.B Stanbury, J.B Wyngaarden, D.S Fredrickson, J.L Goldstein and M.D Brown, Eds.) pp 589-651, McGraw-Hill, New York Breslow, J L (1985) Annu Rev Biochem 54, 699-727 Breslow, J L (1986) in: Biochemistry and Biology of Plasma Lipoproteins (A.M Scanu and A Spector, Eds.) pp 85 - 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390 APOA-11, 294, 364 and LCAT, 314 cDNA, 229, 364 gene, 229, 365 structure and genetic control of, 228 APOA-IV, 178, 365 and LCAT, 314 cDNA, 365, 366 gene, 366 ApoB, 4, 77, 131, 186, 367 abetalipoproteinemia, 369 and arginine residues, 78 cDNA, 368 chemical modification of in LDL, 78 genetic variation, 369 molecular biology of, 81 ApoB-100, 77-93, 139, 162 amino acid composition of, 78 cDNA, 90 cDNA-deduced amino acid sequence, 78 carbohydrate contents of, 80 chemical approach to molecular weight, 78 chromosomal localization of gene, 90 hydrophobicity, 90 immunochemical properties of, 81 mRNA, 90 molecular weight, 78 nucleotide sequence of, 84 - 89 ApOB-26, 77 ApoB-48, 77, 139, 162 in rat, 78 ApoB-74, 77 ApoC, 162 APOC-I, 370 and LCAT, 314 cDNA, 370 gene, 370 APOC-11, 4, 336, 340, 371 and LCAT, 314 cDNA, 371 deficiency, 373 gene structure, 372 400 ApoC-111, 373, 374 and LCAT, 314 cDNA, 374 gene, 375 genetic variation, 375 ApoD, 278 and LCAT, 314 ApoE, 4, 162, 187, 231, 295, 376 accessible conformation of, 187 alleles, 378, 379 and LCAT, 314 cDNA, 377 deficiency, 382 gene structure, 378 inaccessible conformation of, 188 mutations, 378 phenotypes, 378 379, 380 protein polymorphism, 381 thrombin accessible, 188 Apolipoprotein-PC association, thermodynamics of, 110 Apolipoprotein-phospholipidcomplexes, 232 Apolipoproteins amino acid residues, 361 association with human diseases, 360 chromosomal location of genes, 382 - 385 cDNA, 359 gene associated RFLP’s, 387 gene family, 386 - 387 gene mapping, 359 gene mutations, 559 gene rearrangements, 389 - 390 gene structure, 359 gene variation, 359 genomic clones, 359 in lipoproteins, structure of, 103 Arachidonate, 292 Atheromata, 291 Bacterial sepsis, 349 B/E receptor, 161 Bile salt micelles, Blood cells, red, Cachectin, 350 Calculations of particle size, 30 Capillary endothelium, 342 Carbohydrate, 133 Cholecalciferol, 308 Cholesterol distribution, Cholesterol feeding, 161 Cholesterol monohydrate crystals, 12 Cholesterol synthesis, 161 Cholesterol transfer, Cholesterol transport, reverse, I76 Cholesterol, dietary, 3, 171 distribution ratio, 25 intracellular, net movement of, 61 solubility of, 12, 16 Cholesterol/phospholipid ratio, Cholesteryl arachidonate, 292 Cholesteryl ester, core to surface exchange of, 59 exchange proteins (CEEP), fatty acid composition of in humans, 310 hydrolases, 292 products, inhibitory effects of, 319 transfer, 278, 350 transfer, methods of, 282 solubility of, 14 transfer protein (CETP), 278 Cholesteryl linoleyl ether, 350 Cholesteryl oleate, conformation of, 14 Chylomicrons, 1, 77, 153, 335 catabolism of, 154 chemical composition of, compositional changes on entering plasma, composition, lipolysis in rat heart, 56 metabolism, model lymph, 27 nascent, phase equilibria, 31 receptor, 155 remnant receptor, 183, 195 - 197 remnants, 153 size, structure, synthesis of nascent, Chylomicron triglycerides, Circular dichroic spectra, 133 Circular dichroism, 100, 101 spectra, 300 I3C nuclear magnetic resonance (NMR), 13 Core components, 14 Core phase, fraction of total lipid present in, 25 Core remnant, Cycloheximide, 40 f Density gradient ultracentrifugation, 130 Detergent removal, 97 Diethy]@-nitrophenyl) phosphate (E-600), 285, 317 Differential scanning calorimetry (DSC), 13, 97, loo, 101 Diglycerides, 59 Dimyristoyl-phosphatidylcholine(DMPC), 306-307, 311 Dipalmitoyl-phosphatidylcholine (DPPC), 306, 311 Discoidal particles, 282 Disulfide bridges, 132 Distearoyl-phosphatidylcholine (DSPC), 11 Dithionitrobenzoic acid (DTNB), 23 Dysbetalipoproteinemia, 64,293 Egg lecithin, 11 Electron microscopy, 100, 101, 130 Electron spin resonance, 10, 101 Emulsion(s), in vitro lipolytic degradation of, 54 particles, Endogenous protease activity, 131 Endoplasmic reticulum (ER), Endothelial cells, 291 Endothelial surface, 341 Enterocytes, Enthalpy of association, 111 and cholesterol, 114 Equilibrium, of VLDL with erythrocytes, 53 Equilibration of nascent particles with plasma, 52 Erythrocytes, Ether-PC analogs, 308 Fatty acid peroxide, 280 Fatty acids, 3, 59, 279 Fibroblasts, 141, 247 Fluorescence, 100, 101 Fluorescent lipid probes, 281 Foam cells, 183, 198 Free radical process, 280 Frictional coefficient ratio, 302 Functional lipoprotein lipase, 341 Gel filtration chromatography, 130 Glucocorticoids, 347 Glycoprotein, 300, 337 Glycosaminoglycans, 150, 345 Glycosylation, 345 Golgi apparatus, , 344 Golgi complex, 46 Golgi membranes, 46 Guinea pigs, 62, 63 Hep G2 cells, 291 Helical potential, 118 Helical wheel, 116 Heparan sulfate proteoglycan, 345 Heparin, 346 Heparin-releasable lipoprotein lipase, 341 Hepatic lipase, 240 - 242, 348 Hepatic lipoprotein lipase, 342 Hepatic triglyceride lipase, 165 Hepatocytes, 3, 247 High density lipoproteins (HDL), 359 analogs, spherical, chemically defined, 307 and apoA-I, 224 and apoA-11, 224 and CAD, 223, 248-250 and cholesteryl ester, 223, 236 - 237 and triglycerides, 223, 236 - 237 apolipoproteins of, 228 - 230, 237 - 238 apolipoproteins, metabolism of, 243 binding, 176 catabolism, 177, 246 cholesteryl esters, uptake of, 291 components, dynamics of, 235 discoidal, 231 formation of, 231 interaction of with cells,, 246 - 247 intestinal production of, 230 intravascular modification of, 233 liver as source, 230 metabolism, 172 nascent, 172 population distribution of plasma HDL, 221 postprandial phase, 233 precursors of, 231 protein-mediated transfer, 235 reassembled, 121 receptor, 207 - 212 secretory nascent, 231 spherical, 232 spontaneous lipid transfer, 234 structure of, 223 High density lipoprotein (HDL) subclasses, 225, 228 metabolism of, 238 - 242 HDL,, 289, 336 HDL,, biophysical and chemical constituents of, 226 HDL, chemical composition of, 226 HDL,, 224, 227, 289, 336 HDL,, biophysical and chemical constituents of, 226 HDL,, chemical composition of, 226 High performance liquid chromatography (HPLC), 81 Holoenzyme, 347 Homozygous hypobetalipoproteinemia, 369 Hormone-sensitive lipase (L-HSL), 35 Human skin fibroblasts, 291 Hydrophobic moment, 118 Hydrophobic residues, 110 Hydrophobicity, 118 Hydroxymethylglutaryl Coenzyme A reductase (HMG CoA reductase), 14, 41, 171, 186, 247, 261 -265 Hypercholesterolemia, homozygous familial, 155 Hyperlipoproteinemia combined, 167 Type I, 348 Type 111, 58, 162, 380 Type IV, 160 Type V, 154 Hypertriglyceridemia, 183, 290 Type 1, Hypoalphalipoproteinemia, 14 Hypothyroidism, 170 Immunocytochemical localization, 341 Insulin, 347 Intracellular lipolysis, 351 Isoelectric focusing, 132 Isoelectric points, 300 5774 macrophages, 291 Lecithin:cholesterol acyltransferase (LCAT), 7, 98, 164, 232, 278 active site, 321 activity, modulators of, 317 acyl acceptors, 308 acyl donors-fatty acyl chains, 310 acyl donors-glycerol backbone, 309 acyl donors-head groups, 308 affinity for interfaces, 302 amino acid composition of human, 303 and HDL, 304-305 and HDL,, 323 and HDL,, 323 and liver disease, 322 and reverse cholesterol transport, 327 and sulfhydryl reagents, 317 apoA-I/apoD complex, 323 apolipoprotein activators of, 314, 315 cDNA cloning, 328 chemical properties of, 300 deficiency, 324, 325, 326 distribution of activity and mass in human plasma, 323 extrinsic substrate particles, 300 inhibitors, 231 in plasma, 322 intrinsic substrate particles, 300 kinetics and mechanism, 320 mass in plasma, 303 mass, in human plasma, 322 modulators of activity, 318 molar extinction coefficient of, 303 molecular specificity of for phospholipids, 309 molecular substrates, 308 molecular weight, 300 partial specific volume, 300 P C specificity of rat, 313 physical properties of, 300 physiologic role of, 325 purification and assays, 300 reactions, 304 - 305 reactivity of apoA-I PC cholesterol substrates with, 312 role of in HDL, 324 role of in conversion of HDL,, 325 stability of, 302, 317 substrates, 304 - 306 Light scattering, 100, 101 Lipid densities, Lipid distributions in emulsions, calculations of, 25 Lipid lowering drugs cholestyramine, 144 clofibrate, 144 neomycin 144 niacin, 144 Lipid monolayers, 11 403 Lipid surface, 10 permeability of, 109 Lipid transfer protein, 225 activity, 165 Lipid transferlexchange reactions, 50 Lipid-protein association enthalpy of, 110, 11 kinetics of, 106 Lipid-protein interactions, 95 Lipids, 131 core, 10 thermal properties, 15 Lipolysis, 23 1, 286 Lipolytic enzymes, 225 Lipoprotein[a] (Lp[a]), 129, 190 aggregation, 130 association with CAD, 147, 148 catabolism of, 141 contents of, 131 counter-immunoelectrophoresis, 137 electroimmunoassay, 138 enzyme-linked assay (ELSA), 138 hydrated density, 130 immunofluorescence, 141 inheritance pattern, 145 latex immunoassay, 138 model of, 136 molecular weight, 130 radial immunodiffusion, 137 radioimmunoassay, I38 synthesis of, 139 Lipoprotein core, 10 Lipoprotein genetics, 359 and molecular biology, 359 Lipoprotein lipase (LPL), 2, 7, 154, 285, 335 activation, 339 binding, 343 cofactors, 339 deficiency, 340 degradation, 343 distribution, 342 during lactation, 347 endotoxin, 349 extracellular transport, 343 functional molecular weight, 338 genetics of, 348 homology, 338 hormonal control of, 347 maturation, 345 molecular weight, 337 phospholipase A-1, 350 primary structure, 338 receptor, 346 regulation of, 347 sequence, 338 synthesis, 343 Lipoprotein particle diameters, 41 Lipoprotein reassembly, 95, 96 spontaneous, 96, 97 Lipoprotein secretion, Lipoprotein surface, 10 Lipoprotein synthesis, Lipoprotein transport, Lipoproteins nascent, triglyceride-rich, 1, Lipoprotein-X (Lp-X), 324, 326 Liposomes, 290 Low angle X-ray scattering, 101 Low density lipoprotein (LDL) biologically modified, 198 catabolism, 167 endothelial cell (EC)-modified, 198 formation, 166 rnalondialdehyde-derivatized(MDA-LDL), 198 metabolism, 165 modification of by endothelial cells, 198 trypsin-treated, 82 Low density lipoprotein (LDL) receptor, 77, 161, 183-195 pathway, 140 EGF precursor domain, 192 0-linked sugars domain, 192 acetyl-LDL receptor, 197 - 202 cytoplasmic domain, 192 ligand binding domain, 192 membrane-spanning domain, 192 mutations, 172, 193 receptor-binding determinants, 188 regulation of, 194 structure of, 190 Lys residue reagents, 316 Lysosomal degradation, 291 Macrophages, 141, 247 Mannose, 345 Membranes, intracellular, Metastable particle, 64 Mevalonate, 262, 272 404 Mevalonate kinase, 264 Microsomes, 46 Model apolipoproteins, 116 Monesin, 344 Monocyte, 343 Monocyte-derived macrophages, 343 Monocyte-macrophages, 183 Monoglycerides, 3, 59 Monolayer compressibility, 11 Nuclear magnetic resonance (NMR), 100, 101 Neutral lipase, 351 Neutron scattering, 100, 101 N-methylated PE, 308 ob/ob mouse, 344 Obesity, 160 Oligosaccharide, 345 2,3-Oxidosqualene cyclase, 270 Oxysterol, 269 Palmitoyl oleoyl PC (POPC), 31 Pancreatic lipase, 338 cofactors, 339 Puru-chloromercuriphenyl sulfonate, 280 Parenchymal cell, 343 PC/choiesterol molar ratios, 319 Peptides, 15 trypsin-inaccessible, 82 Peroxidase, 341 Phase diagram, 24 Phase diagram analysis, human plasma VLDL, 36 nascent monkey chylomicrons, 36 Phase rule, 25 Phase transition, 97 Phosphatidylcholine, 225, 235, 308 fatty acid composition of in humans, 310 Phospholipid exchange, 280 Phospholipid monolayer, 282 Phospholipid transfer, 282 Phospholipid transfer protein (PTP), 280, 28 Phospholipid vesicles, 13 Phospholipid/triglyceride emulsion, 279 Phospholipids, 284 diacylglycerol, 28 I galactosylcerebroside, 281 hydrophobicity of, 284 phosphatidic acid (PA), 281, 309-313 phosphatidylcholine (PC), 28 1, 309 - 13 phosphatidylethanolamine (PE), 281, 309-313 phosphatidylglycerol (PG), 281, 309 - 31 phosphatidylserine (PS), 281, 309 - 313 sphingomyelin, 281 Polarized light microscopy, 13 Polyacrylamide gel electrophoresis, 132 Polyacrylamide pore gradient gel electrophoresis, 228 Postprandial lipemia, 233, 243 Potentiometric titrations, 100, 101 Proline-rich peptide, 279 Prostacyclin, 292 Prostaglandin E2, 292 Prostanoid, 292 Proteins, transfer, Quasielastic light scattering, 130 Rabbits cholesterol fed, 65 diabetic cholesterol fed, 65 WHHL, 267, 268 Raman spectroscopy, 100, 101 Reassembled lipoproteins, properties of, 100 Receptor-independent removal, 169 Rechromatography, 82 Restriction fragment length polymorphism (RFLP), 387 - 389 Saphenous vein, 149 Sarcoma, 342 Sedimentation coefficient, 302 Sedimentation equilibrium, 130 Sialic acid, 136 Smooth muscle cells, 290 Sodium cholate dialysis method, 306 Sonicated emulsion, 30 Squalene synthetase, 265 Stanazolol, 144 Stereospecificity, 337 Surface phase, fraction of total lipid present in, 25 Synthetic apolipoproteins, 116 Synthetic lipid emulsions, 279 Tangier disease, 18, 232, 314 Tetramethyl urea, 77 - 78 Tie lines, 25 Transitions in lipoprotein, 15 405 Triangular coordinates, 23 Triglyceride exchange of, 278 exchange protein (TGEP), hydrolysis and remnant formation, 53 physical properties, 15 transfer of, 277 transfer inhibitor, CETP, 286 transfer protein, 280 conformation of, 14 core to surface exchange of, 59 crystallization temperature ( T J , 16 Triglyceride-rich lipoproteins, 140, 336 catabolism of, 61 chemical composition, 35 core composition, 32 metabolism, phase diagram analysis of, 44 nascent, 1, 46 phase behavior of subfractions, 40 remnants, 57 remnant formation, 58 remnants in hepatectomized rats, 58 structural features of, structural models of, 18 surface composition, 32 Triolein, solubility of, 13 Triolein-cholesterol-lecithin-water emulsions, 19 Triolein-cholesteryl oleate-cholesterol-lecithinwater emulsions, 27 Triolein-lecithin-water emulsions, 19 Tumor cells, 342 Tumor necrosis factor, 350 Tunicamycin, 345 Ultrasonic irradiation, 96 Very low density proteins (VLDL), 1, 77, 153, 335 beta, 5, 154, 190 bovine plasma, 49 catabolism of, 157 chemical composition of, chicken plasma, 49 cholesterol-enriched hepatic, 63 cholesteryl ester rich, cholesteryl ester-enriched hepatic, 63 composition, composition of, 48 compositional changes on entering plasma, human plasma, 49 hypertriglyceridemic, 65, 183 hypertriglyceridemic S,, 100 - 400, 188 hypertriglyceridemic S,, 20- 60, 188, 189 hypertriglyceridemic S,, 60 - 100, 188 intralipid, 290 kinetics, 158 lipolysis, 55 metabolism, model plasma, 27 nascent hepatic, phase equilibria, 32 rabbit plasma, 49 rat plasma, 49 receptor, beta, 203 - 207 remnants, 153, 285 size, structure, swine plasma, 49 synthesis of nascent, turkey plasma, 49 Vesicles, 284 X-ray diffraction, 13 ... Comprehensive Biochemistry Volume 14 General Editors A NEUBERGER London L.L.M van DEENEN Utrecht ELSEVIER Amsterdam New York - - Oxford V Preface In an earlier volume of New Comprehensive Biochemistry, ... Plasma Lipoproteins Editor A.M GOTTO, Jr Department of Medicine, Baylor College of Medicine, 6335 Fannin, M.S A-601, Houston, TX 77030, USA 1987 ELSEVIER Amsterdam - New York Oxford New Comprehensive. .. Publishing Company, Inc 52 Vanderbilt Avenue New York, NY 10017 (U.S.A.) Library of Congress CataloginginPublication Data Plasma l i p o p r o t e i n s (New comprehensive b io c h e m i s tr y ; v