Efforts to describe and model the molecular structure of biological membranes go back to the beginning of the last century. In 1917, Langmuir described membranes as a layer of lipids one molecule thick [1]. Eight years later, Gorter and Grendel concluded from their studies that "the phospholipid molecules that formed the cell membrane were arranged in two layers to form a lipid bilayer" [2]. Danielli and Robertson proposed, in 1935, a model in which the bilayer of lipids is sequestered between two monolayers of unfolded proteins [3], and the currently still accepted fuid mosaic model was proposed by Singer and Nicolson in 1972 [4]. Among those landmarks of biomembrane history, a serendipitous observation made by Alex Bangham during the early 1960s deserves undoubtedly a special place. His fnding that exposure of dry phospholipids to an excess of water gives rise to lamellar structures [5] has opened versatile experimental access to studying the biophysics and biochemistry of biological phospholipid membranes. Although during the following 4 decades biological membrane models have grown in complexity and functionality [6], liposomes are, besides supported bilayers, membrane nanodiscs, and hybrid membranes, still an indisputably important tool for membrane b- physicists and biochemists. In vol. II of this book, the reader will fnd detailed methods for the use of liposomes in studying a variety of biochemical and biophysical membrane phenomena concomitant with chapters describing a great palette of state-of-the-art analytical technologies.

This volume focuses on recent advances in the biochemical and molecular analysis of different families of phospholipases in plants and their roles in signaling plant growth, development and responses to abiotic and biotic cues. The hydrolysis of membrane lipids by phospholipases produces different classes of lipid mediators, including phosphatidic acid, diacylglycerol, lysophospholipids, free fatty acids and oxylipins. Phospholipases are grouped into different families and subfamilies according to their site of hydrolysis, substrate usage and sequence similarities. Activating one or more of these enzymes often constitutes an early, critical step in many regulatory processes, such as signal transduction, vesicular trafficking, secretion and cytoskeletal rearrangements. Lipid-based signaling plays pivotal roles in plant stress responses, cell size, shape, growth, apoptosis, proliferation, and reproduction.

This book correlates different minerals and lipids serum profiles with the prevalence of cardiovascular disorders in South Asian countries with special emphasis on Pakistan. Cardiovascular disorders (CVD, e.g. coronary heart diseases, hypertension, rheumatic heart disease, angina, heart failure and deep vein thrombosis) show significantly increasing rates in South Asian countries like Pakistan and have become a major health problem. Nevertheless, the data on any aspect of cardiovascular problems still is scanty. The serum profiles of different minerals (copper, magnesium, zinc, selenium) and lipids are analyzed in detail. The presented data will thus lead to a better understanding of the problem and help to provide possible solutions, which can be achieved, e.g. through ameliorated minerals profiles in the daily diet. These results can help develop better dietary management strategies in the prevention and treatment of CVD.

In this second edition methods are described to measure the synthesis of lipids such as the phosphoinositides, ceramides and sphingomyelin, as well as techniques to molecularly characterize the various kinases and phosphatases that regulate the intracellular metabolism of these lipids. Lipid Signaling Protocols, Second Edition guides readers through detailed experimental protocols, which are complimented by review chapters that highlight the technical considerations, challenges and potential pitfalls associated with using these laboratory-based approaches. Written for the Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Lipid Signaling Protocols, Second Edition aims to ensure successful results in the further study of this vital field.

Eicosanoids are a diverse group of biologically active molecules derived from polyunsaturated fatty acid precursors. This volume draws together for the first time a series of overviews on the biosynthesis and functional significance of these and related compounds in a wide range of animals, plants, and micro-organisms. All chapters are written by recognized experts in their fields, and many make use of significant amounts of unpublished materials. This volume is aimed at advanced undergraduates and at researchers interested in lipid biochemistry and general plant and animal biology. Originally published in 1999. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.

Recent studies have shown that cells from adipose tissue are capable of trafficking to tumors, thus enabling paracrine action of adipokines from within the tumor microenvironment. Increased tumor vascularization, immune system suppression and direct effects on malignant cell survival and proliferation have been investigated as mechanisms regulated by adipokines. The goal of this book is to discuss data pointing to the role of adipose tissue in cancer and to dissect individual mechanisms through which adipose tissue excess or restriction could influence cancer progression.

Sphingolipids are lipid components of the plasma membrane of eukaryotic cells with an important function in signaling mechanisms in the cell. This book provides insight into the physiological and pathophysiological role of sphingolipids and in particular its derivative ceramide. The function of Sphingolipids in cell signaling with regard to infectious and lung diseases, cancer, cardiovascular diseases and neuropsychiatric disorders are described and treated in distinct parts. Together with Volume 215 from the same Editors, the collection represents a unique, comprehensive work on Sphingolipids, providing information on both: Sphingolipid basic biology as well as its important function in a (patho)physiological context. The book is written for scientists in pharmacology, biochemistry and cell biology with a focus on biomedical research as well as for clinicians in pharmacology, oncology, cardiology, neurology and infectious disease.

Biomembranes consist of molecular bilayers with many lipid and protein components. The fluidity of these bilayers allows them to respond to different environmental cues by changing their local molecular composition as well as their shape and topology. On the nanometer scale, this multi-responsive behavior can be studied by molecular dynamics simulations, which provide both snapshots and movies of the bilayer conformations. The general conceptual framework for these simulations is provided by the theory of curvature elasticity. The latter theory also explains the behavior of giant vesicles as observed by optical microscopy on the micrometer scale. The present volume describes new insights as obtained from recent developments in analytical theory, computer simulations, and experimental approaches. The seven chapters of the volume are arranged in a bottom-up manner from smaller to larger scales. These chapters address the refined molecular dynamics and multiscale modeling of biomembranes, their morphological complexity and adhesion, the engulfment and endocytosis of nanoparticles, the fusion of giant unilamellar vesicles, as well as recent advances in microfluidic technology applied to model membranes.

Biochemistry of Lipids: Lipoproteins and Membranes, Volume Six, contains concise chapters that cover a wide spectrum of topics in the field of lipid biochemistry and cell biology. It provides an important bridge between broad-based biochemistry textbooks and more technical research publications, offering cohesive, foundational information. It is a valuable tool for advanced graduate students and researchers who are interested in exploring lipid biology in more detail, and includes overviews of lipid biology in both prokaryotes and eukaryotes, while also providing fundamental background on the subsequent descriptions of fatty acid synthesis, desaturation and elongation, and the pathways that lead the synthesis of complex phospholipids, sphingolipids, and their structural variants. Also covered are sections on how bioactive lipids are involved in cell signaling with an emphasis on disease implications and pathological consequences.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases - and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.

The scientific advances in the physiology and pathophysiology of adipose tissue over the last two decades have been considerable. Today, the cellular and molecular mechanisms of adipogenesis are well known. In addition, adipose tissue is now recognized as a real endocrine organ that produces hormones such as the leptin acting to regulate food intake and energy balance in the central nervous system, a finding that has completely revolutionized the paradigm of energy homeostasis. Other adipokines have now been described and these molecules are taking on increasing importance in physiology and pathophysiology. Moreover, numerous works have shown that in obesity, but also in cases of lipodystophy, adipose tissue was the site of a local low-grade inflammation that involves immune cells such as macrophages and certain populations of lymphocytes. This new information is an important step in the pathophysiology of both obesity and related metabolic and cardiovascular complications. Finally, it is a unique and original work focusing on adipose tissue, covering biology and pathology by investigating aspects of molecular and cellular biology, general, metabolic, genetic and genomic biochemistry.

Presents a multi-disciplinary perspective on the physics of life and the particular role played by lipids and the lipid-bilayer component of cell membranes. Emphasizes the physical properties of lipid membranes seen as soft and molecularly structured interfaces. By combining and synthesizing insights obtained from a variety of recent studies, an attempt is made to clarify what membrane structure is and how it can be quantitatively described. Shows how biological function mediated by membranes is controlled by lipid membrane structure and organization on length scales ranging from the size of the individual molecule, across molecular assemblies of proteins and lipid domains in the range of nanometers, to the size of whole cells. Applications of lipids in nano-technology and biomedicine are also described.

For years lipids have fascinated cell biologists and biochemists due to their profound effects on cell function. "Cellular Lipid Metabolism" highlights new concepts and recent findings, but also reviews important discoveries made in the past. Outstanding international experts contribute 13 chapters on the genetics, molecular and cell biology of lipids. Presenting analyses at the molecular level they reveal the principles by which cellular lipid metabolism functions. Further, numerous intriguing observations that cannot yet be explained are identified, stimulating the readers to future studies. This book provides an invaluable source of information for biomedical researchers in energy metabolism, vascular biology, endocrinology and lipidology.

Lipid Signaling Protocols assembles in a single volume the various tools and methodologies needed by the interested investigator to unravel lipid dependent signaling and cell function. Divided into two convenient sections, the volume begins by summarizing the physical properties of hydrophobic metabolites as well as the physical methodologies used for their analysis, which leads to the second section and its selection of biological methods, focused around the most relevant lipids, their corresponding metabolizing enzymes and the recognition proteins. Following the highly successful Methods in Molecular Biology (TM) series format, the chapters provide readily reproducible laboratory protocols, lists of necessary materials and reagents, and the tips on troubleshooting and avoiding known pitfalls. Contributed to by top researchers in the field, Lipid Signaling Protocols is an essential resource for both experienced and novice researchers who desire a better understanding of the application of physical methodologies in the context of lipid signaling and lipid metabolism in cell biology.

Although previously thought to be merely passive structural components, membrane lipids have recently been found to be actively involved in cellular transport and signal transduction processes. Clear protocols for the study of membrane lipid properties, cellular transport or signal transduction are presented in this manual. Following a short introduction to membrane lipids, techniques for the isolation and extraction of membrane fractions, the analysis of the lipid composition, lipid turnover, and the involvement in signal transduction as well as the preparation of liposomes are described.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases - and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

Lipids can usually be extracted easily from tissues by making use of their hydrophobic characteristics. However, such extractions yield a complex mixture of different lipid classes which have to be purified further for quantitative analysis. Moreover, the crude lipid extract will be contami nated by other hydrophobic molecules, e.g. by intrinsic membrane proteins. Of the various types of separation processes, thin layer and column chromatography are most useful for intact lipids. High performance liquid chromatography (HPLC) is also rapidly becoming more popular, especially for the fractionation of molecular species of a given lipid class. The most powerful tool for quantitation of the majority of lipids is gas liquid chromatography (GLC). The method is very sensitive and, if adapted with capillary columns, can provide information with regard to such subtle features as the position or configuration of substitutions along acyl chains. By coupling GLC or HPLC to a radioactivity detector, then the techniques are also very useful for metabolic measurements. Although research laboratories use generally sophisticated analytical methods such as GLC to analyse and quantify lipid samples, chemical derivatii: ations are often used in hospitals. For these methods, the lipid samples are derivatized to yield a product which can be measured simply and accurately"- usually by colour. Thus, total triacylglycerol, cholesterol or phospholipid-phosphorus can be quantitated conveniently without bothering with the extra information of molecular species, etc. which might be determined by more thorough analyses. REFERENCES Christie, W.W. (1982) Lipid Analysis, 2nd edn, Pergamon Press, Oxford."

Interest in and emphasis upon different aspects of the sphingolipids have, in general, followed the biochemical developments of the day. The early inves- tigators were preoccupied principally with the isolation of "pure" compounds and structural elucidation. This historical perspective is found in the discus- sion presented in Chapter 1 (Section 1. 1. 2 and Table III). Still, the isolation and structural characterization of glycolipids are the basic foundation of all our knowledge of enzymology, immunology, and cell biology. Recent infor- mation obtained on structure has greatly affected the interpretation of various phenomena related to glycolipids. New structures suggest a new role of gly- colipids as antigens and receptors. Ten years ago, only four neutral glycolipids and two gangliosides were known in human erythrocytes. We now know structures of at least twenty additional neutral glycolipids and ten additional gangliosides in human erythrocytes that are known to be important blood group, heterophil, and autoantigens. Erythrocytes are only one example of a cell type whose glycolipid profile has been extensively studied. Our defective knowledge in immunology and cell biology may be due to incomplete un- derstanding of structural chemistry. Modern methodology based on methyla- tion analysis, mass spectrometry, and enzymatic degradation has supple- mented classical analysis based on clorimetry. Nuclear magnetic resonance spectroscopy is still in the development stage, but will eventually replace var- ious chemical analyses. However, important future studies should be directed toward elucidating the organizational structure of glycolipids in membranes.

Many of the desirable flavour and textural attributes of dairy products are due to their lipid components; consequently, milk lipids have, tradi tionally, been highly valued, in fact to the exclusion of other milk components in many cases. Today, milk is a major source of dietary lipids in western diets and although consumption of milk fat in the form of butter has declined in some countries, this has been offset in many cases by increasing consumption of cheese and fermented liquid dairy products. This text on milk lipids is the second in a series entitled Developments in Dairy Chemistry, the first being devoted to milk proteins. The series is produced as a co-ordinated treatise on dairy chemistry with the objective of providing an authoritative reference source for lecturers, researchers and advanced students. The biosynthesis, chemical, physical and nutritional properties of milk lipids have been reviewed in eight chapters by world experts. However, space does not permit consideration of the more product-related aspects of milk lipids which play major functional roles in several dairy products, especially cheese, dehydrated milks and butter.

Efforts to describe and model the molecular structure of biological membranes go back to the beginning of the last century. In 1917, Langmuir described membranes as a layer of lipids one molecule thick [1]. Eight years later, Gorter and Grendel concluded from their studies that "the phospholipid molecules that formed the cell membrane were arranged in two layers to form a lipid bilayer" [2]. Danielli and Robertson proposed, in 1935, a model in which the bilayer of lipids is sequestered between two monolayers of unfolded proteins [3], and the currently still accepted fuid mosaic model was proposed by Singer and Nicolson in 1972 [4]. Among those landmarks of biomembrane history, a serendipitous observation made by Alex Bangham during the early 1960s deserves undoubtedly a special place. His fnding that exposure of dry phospholipids to an excess of water gives rise to lamellar structures [5] has opened versatile experimental access to studying the biophysics and biochemistry of biological phospholipid membranes. Although during the following 4 decades biological membrane models have grown in complexity and functionality [6], liposomes are, besides supported bilayers, membrane nanodiscs, and hybrid membranes, still an indisputably important tool for membrane b- physicists and biochemists. In vol. II of this book, the reader will fnd detailed methods for the use of liposomes in studying a variety of biochemical and biophysical membrane phenomena concomitant with chapters describing a great palette of state-of-the-art analytical technologies.

This volume represents the first attempt to present in one place the clinical syndromes and the pathophysiologic basis for the "resistance states" to each of the classes of steroid hormones. Glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone and vitamin D have widely diverse roles ranging from the control of homeostasis to reproduction and bone formation. They are similar in that they share a chemical structure and that their action is in the cell nucleus where they induce transcription of specific genes leading to synthesis of function-specific proteins. Clinical syndromes of steroid hormone resistance to androgens (complete and partial testicular feminization), aldosterone (pseudo hypoaldosteronism) and vitamin D (vitamin D-dependent rickets type II) have been known for many years. Progesterone and glucocorticoid resistance syndromes have been described only recently. Resistance to estrogens has not been reported in man or in animals. It is hoped that a detailed reexamination of what is known about each of these conditions at the clinical and molecular levels will enhance our understanding of the function of these hormones and their mechanisms of action. New insight and research initiatives should result. G.P. Chrousos D.L. Loriaus M.B. Lipsett vii ACKNOWLEDGMENTS The contents of this volume are based in part on the proceedings of an International Conference held in Bethesda in the summer of 1984. This conference was sponsored by the National Institute of Child Health and Human Development, Bethesda, Maryland."

Themulticomponentnatureofbiologicalmembranesandtheirintra- andextracel- lar interactions make direct investigations on the membrane structure and processes nearly impossible. Clearly, a better understanding of the membrane properties and the mechanisms determining membrane protein functions is crucial to the imp- mentation of biosensors, bioreactors and novel platforms for medical therapy. For this reason, the interest in model systems suitable for the construction and study of complex lipid/protein membrane architectures has increased steadily over the years. The classical portfolio of model membranes used for biophysical and - terfacial studies of lipid (bi)layers and lipid/protein composites includes Langmuir monolayers assembled at the water/air interface, (uni- and multi-lamellar) vesicles in bulk (liposomal) dispersion, bimolecular lipid membranes (BLMs), and various types of solid-supported membranes. All these have speci?c advantages but also suffer from serious drawbacksthat limit their technical applications. Polymer m- branes comprised of entirely synthetic or hybrid (synthetic polymer/biopolymer) block copolymersappeared to be an attractive alternative to the lipid-based models. Generally, the synthetic block copolymer membranes are thicker and more stable and the versatility of polymer chemistry allows the adoption of relevant properties for a wide range of applications. This volume provides a vast overview of the physico-chemical and synthetic - pectsofarti?cial membranes. Numerousmembranemodelsaredescribed,including their properties(i. e. swelling, drying,lateral mobility,stability, electrical conduct- ity, etc. ), advantages, and drawbacks. The potential applications of these models are discussed and supported by real examples. Chapter 1 summarizesmethodsfor the stabilizationof arti?cial lipid membranes.

In the preface to the Second edition, we made a prediction that many exciting developments would take place in the coming years that would change the face of a new edition. This has indeed been the case and the current edition reflects these new advances. Our picture of the structure of the fatty acid synthetase has changed dramatically, bringing a new concept in enzymology - the multicatalytic polypeptide chain. This new knowledge owes much to the exploitation of genetic mutants, the use of which is undoubtedly going to extend into many other areas of lipid biochemistry. An understanding of the control of lipid metabolism has also advanced considerably during the last decade and we have tried to reflect that here, although it will be some years before a truly integrated picture can be obtained. For this reason we have continued to deal with the control of particular aspects of lipid metabolism - fatty acids, triacylglycerols, lipoprotein- in the specific chapters but we can foresee the time when a chapter on the overall integration of lipid metabolism will be appropriate and feasible. As a particular example, the exciting new concepts of the control of cholesterol metabolism in specific tissues via the interaction of low density lipoproteins with cell surface receptors have been described in Chapter 6.

Knowledge of cholesterol and its interaction with protein molecules is of fundamental importance in both animal and human biology. This book contains 22 chapters, dealing in depth with structural and functional aspects of the currently known and extremely diverse unrelated families of cholesterol-binding and cholesterol transport proteins. By drawing together this range of topics the Editor has attempted to correlate this broad field of study for the first time. Technical aspects are given considerable emphasis, particularly in relation cholesterol reporter molecules and to the isolation and study of membrane cholesterol- and sphingomyelin-rich "raft" domains. Cell biological, biochemical and clinical topics are included in this book, which serve to emphasize the acknowledged and important benefits to be gained from the study of cholesterol and cholesterol-binding proteins within the biomedical sciences and the involvement of cholesterol in several clinical disorders. It is hoped that by presenting this topic in this integrated manner that an appreciation of the fact that there is much more that needs to be taken into account, studied and understood than the widely discussed "bad and good cholesterol" associated, respectively, with the low- and high-density lipoproteins, LDL and HDL.

A symposium was centered around the unsaturated phosphatidyl- choline molecule and organized in order to assemble and coordi- nate theoretical views with facts and results. The presence of a high percentage of essential fatty acids in unsaturated phos- phatidylcholine gave rise to the essential phospholipid concept. An overview of the biological significance of phospholipids and a review of a specific phosphatidylcholine-related enzyme, namely LCAT or lecithin cholesterol acyl transferase, open these proceedings. The simultaneous use of the synonyms - leci- thin and phosphatidylcholine - was solved throughout the pub- lished material by a preferential use of the more precise che- mical terminology of phosphatidylcholine. A set of papers centered around the pharmacology of polyunsa- turated phosphatidylcholine (PU-PC) or essential phospholipids (EPL) is followed by reports on its therapeutic effects. Further papers deal with the metabolism of the arterial wall and the presence of phospholipid related enzyme systems. Some hemody- namic related effects are dealt with in the last section. These proceedings could be edited within a few months thanks to the active cooperation of the authors. The editors are grateful to acknowledge this rather unusual performance which tends to prove the interest of all participants in this sym- posium. It seems logical to presume that the topic itself is an important one and that the meeting was timely organized.