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Abbreviations | |
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Preface | |
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Acknowledgements | |
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Lipids: definition, isolation, separation and detection | |
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Introduction | |
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Definitions | |
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Structural chemistry and nomenclature | |
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Extraction of lipids from natural samples | |
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Likely components of the crude lipid extract | |
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General features of lipids important for their analysis | |
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Chromatographic techniques for separating lipids | |
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The two phases can be arranged in a variety of ways | |
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Gas-liquid chromatography is a particularly useful method for volatile derivatives of lipids | |
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Absorption column chromatography is used for the separation of large amounts of lipids | |
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Thin layer absorption chromatography can achieve very good separation of small lipid samples | |
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Other useful methods | |
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Summary | |
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Further Reading | |
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Fatty acid structure and metabolism | |
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Structure and properties | |
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Saturated fatty acids | |
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Branched-chain fatty acids | |
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Unsaturated fatty acids | |
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Monoenoic (monounsaturated) fatty acids | |
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Polyenoic (polyunsaturated) fatty acids | |
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Cyclic fatty acids | |
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Oxy acids | |
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Conjugated unsaturated fatty acids | |
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Fatty aldehydes and alcohols | |
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Some properties of fatty acids | |
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Quantitative and qualitative fatty acid analysis | |
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General principles | |
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Determination of the structure of an unknown acid | |
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The biosynthesis of fatty acids | |
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Conversion of fatty acids into metabolically active thiolesters is often a prerequisite for their metabolism | |
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Acyl-CoA thiolesters were the first types of activated fatty acids to be discovered | |
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Acyl-acyl carrier proteins can be formed as distinct metabolic intermediates in some organisms | |
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The biosynthesis of fatty acids can be divided into de novo synthesis and modification reactions | |
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De novo biosynthesis | |
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Acetyl-CoA carboxylase | |
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Fatty acid synthase | |
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Termination | |
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Elongation | |
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Branched-chain fatty acids | |
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The biosynthesis of hydroxy fatty acids results in hydroxyl groups in different positions along the fatty chain | |
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The biosynthesis of unsaturated fatty acids is mainly by oxidative desaturation | |
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Monounsaturated fatty acids | |
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Polyunsaturated fatty acids | |
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Formation of polyunsaturated fatty acids in animals | |
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Biohydrogenation of unsaturated fatty acids takes place in rumen microorganisms | |
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The biosynthesis of cyclic acids provided one of the first examples of a complex lipid substrate for fatty acid modifications | |
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The control of fatty acid synthesis can take place at a number of enzyme steps | |
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Acetyl-CoA carboxylase (ACC) regulation in animals | |
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Acetyl-CoA carboxylase regulation in other organisms | |
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Regulation of fatty acid synthase | |
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Control of animal desaturases | |
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Degradation of fatty acids | |
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[beta]-Oxidation is the most common type of biological oxidation of fatty acids | |
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Cellular site of [beta]-oxidation | |
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Transport of acyl groups to the site of oxidation: the role of carnitine | |
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Control of acylcarnitine formation is very important | |
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Enzymes of mitochondrial [beta]-oxidation | |
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Other fatty acids containing branched chains, double bonds and an odd number of carbons atoms can also be oxidized | |
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Regulation of mitochondrial [beta]-oxidation | |
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Fatty acid oxidation in E. coli | |
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[beta]-Oxidation in microbodies | |
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[alpha]-Oxidation of fatty acids is important when structural features prevent [beta]-oxidation | |
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[omega]-Oxidation uses mixed-function oxidases | |
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Chemical peroxidation is an important reaction of unsaturated fatty acids | |
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Peroxidation catalysed by lipoxygenase enzymes | |
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Lipoxygenases are important for stress responses and development in plants | |
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Essential fatty acids and the biosynthesis of eicosanoids | |
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The pathways for prostaglandin synthesis are discovered | |
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Cyclic endoperoxides can be converted into different types of eicosanoids | |
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New eicosanoids are discovered | |
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The cyclooxygenase products exert a range of activities | |
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Prostaglandins and other eicosanoids are rapidly catabolized | |
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Instead of cyclooxygenation, arachidonate can be lipoxygenated or epoxygenated | |
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Control of leukotriene formation | |
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Physiological action of leukotrienes | |
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For eicosanoid synthesis an unesterified fatty acid is needed | |
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Essential fatty acid activity is related to double bond structure and to the ability of such acids to be converted into a physiologically active eicosanoid | |
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Summary | |
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Further Reading | |
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Lipids as energy stores | |
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Introduction | |
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The naming and structure of the acylglycerols (glycerides) | |
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Triacylglycerols are the major components of natural fats and oils; partial acylglycerols are usually intermediates in the breakdown or synthesis of triacylglycerols | |
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All natural oils are complex mixtures of molecular species | |
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The storage of triacylglycerols in animals and plants | |
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Adipose tissue depots are the sites of TAG storage in animals | |
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Milk triacylglycerols provide a supply of energy for the needs of the new-born | |
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Some plants use lipids as a fuel, stored as minute globules in the seed | |
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The biosynthesis of triacylglycerols | |
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Pathways for complete (de novo) synthesis build-up TAG from small basic components | |
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The glycerol 3-phosphate pathway in mammalian tissues provides a link between TAG and phospholipid metabolism | |
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The dihydroxyacetone phosphate pathway in mammalian tissues is a slight variant to the main glycerol 3-phosphate pathway and provides an important route to ether lipids | |
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Formation of triacylglycerols in plants involves the co-operation of different subcellular compartments | |
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The monoacylglycerol pathway is important mainly in rebuilding TAG from absorbed dietary fat | |
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The catabolism of acylglycerols | |
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The nature and distribution of lipases | |
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Animal triacylglycerol lipases play a key role in the digestion of food and in the uptake and release of fatty acids by tissues | |
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Plant lipases break down the lipids stored in seeds in a specialized organelle, the glyoxysome | |
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The integration and control of animal acylglycerol metabolism | |
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Fuel economy: the interconversion of different types of fuels is hormonally regulated to maintain blood glucose concentration within the normal range and ensure storage of excess dietary energy in triacylglycerols | |
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The control of acylglycerol biosynthesis is important, not only for fuel economy but for membrane formation, requiring close integration of storage and structural lipid metabolism | |
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Mobilization of fatty acids from fat stores is regulated by hormonal balance, which in turn is responsive to nutritional and physiological states | |
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Wax esters | |
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Occurrence and characteristics | |
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Biosynthesis of wax esters involves the condensation of a long-chain fatty alcohol with fatty acyl-CoA | |
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Digestion and utilization of wax esters is poorly understood | |
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Surface lipids include not only wax esters but a wide variety of lipid molecules | |
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Summary | |
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Further Reading | |
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Dietary lipids | |
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Lipids in food | |
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The fats in foods are derived from the structural and storage fats of animals and plants | |
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The fatty acid composition of dietary lipids depends on the relative contributions of animal and plant structural or storage lipids | |
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Industrial processing may influence the chemical and physical properties of dietary fats either beneficially or adversely | |
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Catalytic hydrogenation | |
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Heating | |
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Irradiation | |
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Interesterification | |
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Fractionation | |
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Structured fats | |
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A few dietary lipids may be toxic | |
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Cyclopropenes | |
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Long-chain monoenes | |
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Trans-unsaturated fatty acids | |
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Lipid peroxides | |
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Roles of dietary lipids | |
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Triacylglycerols provide a major source of metabolic energy especially in affluent countries | |
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Lipids supply components of organs and tissues for membrane synthesis and other functions | |
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Foetal growth | |
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Post-natal growth | |
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Dietary lipids supply essential fatty acids that are essential to life but cannot be made in the animal body | |
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Historical background: discovery of essential fatty acid deficiency | |
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Biochemical basis for EFA deficiency | |
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Functions of essential fatty acids | |
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Which fatty acids are essential? | |
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What are the quantitative requirements for essential fatty acids in the diet? | |
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Dietary lipids supply fat-soluble vitamins | |
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Vitamin A | |
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Vitamin D | |
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Vitamin E | |
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Vitamin K | |
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Lipids play an important role in enhancing the flavour and texture and therefore the palatability of foods | |
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Odour | |
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Taste | |
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Texture | |
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Dietary lipids in relation to immune function | |
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Components of the immune system and their functional assessment | |
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Summary of lipid effects on different components of immunity | |
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Influence on target cell composition | |
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Influence on lymphocyte functions ex vivo | |
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Influence on antibody production | |
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Influence on delayed-type hypersensitivity | |
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Graft versus host and host versus graft reactions and organ transplants | |
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Survival after infection | |
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Influence on autoimmune and inflammatory disease processes | |
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Mechanisms | |
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Membrane properties | |
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Availability of eicosanoid precursors | |
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Availability of vitamin E | |
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Gene expression | |
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Implications for dietary advice | |
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Lipids and cancer | |
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Dietary lipids and cancer | |
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Cellular lipid changes in cancer | |
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Lipids and the treatment of cancer | |
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Summary | |
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Further Reading | |
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Lipid transport | |
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Digestion and absorption | |
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Intestinal digestion of dietary fats involves breakdown into their component parts by a variety of digestive enzymes | |
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The intraluminal phase of fat absorption involves passage of digestion products into the absorptive cells of the small intestine | |
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The intracellular phase of fat absorption involves recombination of absorbed products in the enterocytes and packaging for export into the circulation | |
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Malassimilation of lipids, through failure to digest or absorb lipids properly, can arise from defects in the gut or other tissues but may also be induced deliberately | |
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Transport of lipids in the blood: plasma lipoproteins | |
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Lipoproteins can be conveniently divided into groups according to density | |
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The apolipoproteins are the protein moieties that help to stabilize the lipid; they also provide specificity and direct the metabolism of the lipoproteins | |
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The different classes of lipoprotein particles transport mainly triacylglycerols or cholesterol through the plasma | |
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Specific lipoprotein receptors mediate the cellular removal of lipoproteins and of lipids from the circulation | |
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Membrane receptors | |
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The LDL-receptor | |
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The LDL-receptor-related protein and other members of the LDL-receptor family | |
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Scavenger receptors | |
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The lipoprotein particles transport lipids between tissues but they interact and are extensively remodelled in the plasma compartment | |
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Species differ quantitatively in their lipoprotein profiles | |
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The co-ordination of lipid metabolism in the body | |
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The sterol regulatory element binding protein (SREBP) system controls pathways of cholesterol accumulation in cells and may also control fatty acid synthesis | |
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The peroxisome proliferator activated receptor (PPAR) system regulates fatty acid metabolism in liver and adipose tissue | |
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Other nuclear receptors are activated by fatty acids and affect gene expression | |
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Adipose tissue secretes hormones and other factors that may themselves play a role in regulation of fat storage | |
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Diseases involving changes or defects in lipid metabolism | |
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Atherosclerosis | |
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Risk factors for CHD and the effects of diet | |
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Hyperlipoproteinaemias (elevated circulating lipoprotein concentrations) are often associated with increased incidence of cardiovascular disease | |
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Obesity and diabetes are associated with increased risk of cardiovascular diseases | |
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Hypolipoproteinaemias are rare conditions of abnormally low plasma lipoprotein concentrations | |
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Summary | |
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Further Reading | |
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Lipids in cellular structures | |
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Cell organelles | |
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Glycerolipids | |
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Phosphoglycerides are the major lipid components of most biological membranes | |
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Phosphonolipids constitute a rare class of lipids found in few organisms | |
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Glycosylglycerides are particularly important components of photosynthetic membranes | |
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Betaine lipids are important in some organisms | |
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Ether-linked lipids and their bioactive species | |
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Sphingolipids | |
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Sterols | |
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Major sterols | |
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Other steroids | |
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Membrane structure | |
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Early models already envisaged a bilayer of lipids but were uncertain about the location of the proteins | |
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The lipid-globular protein mosaic model now represents the best overall picture of membrane structure | |
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Membrane structure is not static but shows rapid movement of both lipid and protein components | |
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Further remarks on the lipid composition of membranes | |
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Transbilayer asymmetry is an essential feature of all known biological membranes | |
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Lateral heterogeneity is probably important in some membranes at least | |
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Physical examination of membranes reveals their fluid properties | |
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General functions of membrane lipids | |
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Membrane lipids are modified to maintain fluidity at low temperatures | |
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Lipids and membrane fusion | |
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Lipids and proteins interact in order to determine membrane structure and shape | |
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Why are there so many membrane lipids? | |
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Liposomes and drug delivery systems | |
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Lipid anchors for proteins | |
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Acylation | |
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Prenylation | |
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GPI-anchors | |
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Lipids as components of the surface layers of different organisms | |
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Cutin, suberin and waxes - the surface coverings of plants | |
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Mycobacteria contain specialized cell-wall lipids | |
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Lipopolysaccharide forms a major part of the cell envelope of Gram-negative bacteria | |
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Gram-positive bacteria have a completely different surface structure | |
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Insect waxes | |
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Lipids of the skin--the mammalian surface layer and skin diseases | |
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Summary | |
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Further Reading | |
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Metabolism of structural lipids | |
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Phosphoglyceride biosynthesis | |
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Tracer studies revolutionized concepts about phospholipids | |
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Formation of the parent compound, phosphatidate, is demonstrated | |
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A novel cofactor for phospholipid synthesis was found by accident | |
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The core reactions of glycerolipid biosynthesis are those of the Kennedy pathway | |
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The zwitterionic phosphoglycerides can be made using CDP-bases | |
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CDP-diacylglycerol is an important intermediate for phosphoglyceride formation in all organisms | |
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Phospholipid formation in E. coli is entirely via CDP-diacylglycerol | |
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Differences between phosphoglyceride synthesis in different organisms | |
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Plasmalogen biosynthesis | |
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Platelet activating factor (PAF): a biologically active phosphoglyceride | |
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Degradation of phospholipids | |
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General features of phospholipase reactions | |
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Phospholipase A activity is used to remove a single fatty acid from intact phospholipids | |
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Phospholipase B and lysophospholipases | |
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Phospholipases C and D remove water-soluble moieties | |
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Phospholipids may also be catabolized by non-specific enzymes | |
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Metabolism of glycosylglycerides | |
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Biosynthesis of galactosylglycerides takes place in chloroplast envelopes | |
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Catabolism of glycosylglycerides | |
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Relatively little is known of the metabolism of the plant sulpholipid | |
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Metabolism of sphingolipids | |
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Biosynthesis of the sphingosine base and ceramide | |
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Cerebroside biosynthesis | |
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Formation of neutral glycosphingolipids | |
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Ganglioside biosynthesis | |
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Sulphated sphingolipids | |
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Sphingomyelin is both a sphingolipid and a phospholipid | |
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Catabolism of the sphingolipids | |
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Cholesterol biosynthesis | |
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Acetyl-CoA is the starting material for terpenoid as well as fatty acid synthesis | |
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Further metabolism generates the isoprene unit | |
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Higher terpenoids are formed by a series of condensations | |
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A separate way of forming the isoprene unit occurs in plants | |
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Sterol synthesis requires cyclization | |
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Cholesterol is an important metabolic intermediate | |
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It is important that cholesterol concentrations in plasma and tissues are regulated within certain limits and complex regulatory mechanisms have evolved | |
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Specific roles | |
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Pulmonary surfactant | |
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Lipid storage diseases (lipidoses) | |
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The 'phosphatidylinositol cycle' in cell signalling | |
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A wider range of lipid signalling molecules | |
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Phospholipase D in cell signalling | |
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Role of sphingolipids in cellular signalling | |
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Summary | |
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Further Reading | |
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Index | |