The Fats of Life The Fats of Life Essential Fatty Acids in Health and Disease GLEN D. LAWRENCE RUTGERS UNIVERSITY PRESS NEW BRUNSWICK, NEW JERSEY, AND LONDON LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA Lawrence, Glen D., 1948– The fats of life : essential fatty acids in health and disease / Glen D. Lawrence. p. cm. Includes bibliographical references and index. ISBN 978–0-8135–4677–3 (hardcover : alk. paper) 1. Fatty acids in human nutrition. 2. Essential fatty acids—Physiological effect. I. Title. II. Title: Essential fatty acids in health and disease. [DNLM: 1. Fatty Acids, Essential—metabolism. 2. Diet. 3. Dietary Fats—metabolism. 4. Health Behavior. 5. Nervous System—metabolism. QU 90 L421f 2010] QP752.F35L39 2010 612.3'97—dc22 2009020397 CIP A British Cataloging-in-Publication record for this book is available from the British Library. Copyright © 2010 by Glen D. Lawrence All rights reserved No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, or by any information storage and retrieval system, without written permission from the publisher. Please contact Rutgers University Press, 100 Joyce Kilmer Avenue, Piscataway, NJ 08854–8099. The only exception to this prohibition is “fair use” as defi ned by U.S. copyright law. Visit our Web site: http://rutgerspress.rutgers.edu Manufactured in the United States of America CONTENTS List of Figures vii List of Tables ix Preface xi List of Abbreviations xv PART ONE Nutritional, Chemical, and Physiological Properties of Dietary Fats 1 The Dietary Fat Doctrine 3 2 Lipid Terminology, Structure, and Function 15 3 Some Dietary Fats Are Essential 33 4 Signals, Messengers, and Responses 44 5 Oxidation and Lipid Peroxidation 60 PART TWO Dietary Fats in Health and Disease 6 Atherosclerosis 73 7 Risk Factors in Cardiovascular Disease 88 8 Lipid-Lowering Drugs 96 9 Infl ammation, Anti-infl ammatory Drugs, 107 and Lipid Mediators 10 Cancer and Immunity 122 11 Neurological Development, Memory, and Learning 138 12 Functional Disorders of the Nervous System 152 13 Neurodegenerative Diseases 166 v vi CONTENTS PART THREE Infl uence of Diet on Overall Health 14 Obesity: Health Consequences and Dietary Infl uences 183 15 Dietary Choices for Comprehensive Health 201 Appendix A Fundamentals of Chemical Bonding and Polarity 215 Appendix B Fatty Acid Composition of Dietary Fats and Oils 219 Appendix C Chemical Structures of Eicosanoids 222 Appendix D Human Lipoproteins: Their Components, 225 Properties, and Associated Proteins Appendix E Overview of Neuronal Processes 228 Glossary 235 References 249 Index 271 FIGURES 2.1. Four fatty acids 17 2.2. The essential fatty acids 19 2.3. Two triglycerides 20 2.4. Metabolism of linoleic acid to arachidonic acid 22 2.5. Lecithin 23 2.6. Structures of sphingosine and some sphingolipids 24 2.7. Two phosphatides and a phospholipid membrane 25 2.8. The splitting of a phospholipid by phospholipase A2 28 3.1. Metabolism of linolenic acid to docosahexaenoic acid 35 3.2. Metabolism of arachidonic acid to bioactive eicosanoids 36 4.1. The four major receptors for epinephrine and norepinephrine 47 4.2. Splitting of phosphatidyl inositol-4,5-bisphosphate 49 by phospholipase C 4.3. The action of steroid hormones on their nuclear receptors 50 4.4. The role of thromboxane A2 and prostacyclin 53 in vascular homeostasis and thrombosis 4.5. Structures of some endocannabinoids 55 5.1. Superoxide anion reacts with hydrogen peroxide 63 to produce hydroxyl radical 5.2. Scheme for lipid peroxidation of linoleic acid 66 5.3. The consequences of oxidative stress on cell membranes, 68 lipoproteins, and DNA 6.1. Atherogenesis 75 6.2. Products formed by oxidation of arachidonate in phospholipids 77 of LDL 6.3. Foam cells in fatty streaks are accessible to apolipoproteins 82 6.4. Lipid oxidation products induce transformation 83 of vascular cells to calcifying-type cells 6.5. Infi ltration by activated leukocytes releases proteases 84 and breaks down the fi brous cap 8.1. Chemical structures of HMGCoA and several common statin drugs 99 9.1. Conversion of salicylic acid to aspirin 108 vii viii FIGURES 9.2. Synthesis of prostaglandins and thromboxanes 109 from arachidonic acid 9.3. Most NSAIDs inhibit both COX-1 and COX-2 112 9.4. Metabolism of arachidonic acid and EPA 114 by aspirin-modifi ed COX-2 9.5. Physiological actions of prostaglandin E2. 115 9.6. Steroids inhibit release of arachidonic acid 120 from membrane phospholipids 10.1. Carcinogenesis 124 10.2. Angiogenesis can be inhibited by NSAIDs 128 and COX-2 inhibitors 10.3. NSAIDs can promote apoptosis by suppression 129 of prostaglandin E2 production 10.4. Structures of vaccenic acid, linoleic acid, and two 130 of its conjugated isomers 10.5. Anticancer effects of conjugated linoleic acid 132 10.6. Production of mevalonate is inhibited by statin drugs 136 14.1. Relationship of body mass index to hypertension 184 and high blood cholesterol 14.2. Metabolic consequences of lack of exercise and high sugar 197 consumption A.1. Normal bonding in organic chemistry 215 A.2. Saturated and unsaturated molecules 216 A.3. Neutral molecules 216 A.4. Molecular polarity 217 C.1. Eicosanoids synthesized from arachidonic acid 222 C.2. Eicosanoids synthesized from eicosapentaenoic acid 223 C.3. Eicosanoids synthesized from dihomo-gamma-linolenic acid 224 D.1. Schematic illustration of a lipoprotein particle 226 E.1. Enzymatic conversion of glutamate to GABA 228 E.2. Neuronal excitation 229 E.3. Basic structure of a neuron 230 E.4. Ions and depolarization 231 E.5. Synaptic transmission 232 TABLES 11.1. Important considerations regarding essential fatty acid status 146 of mother and child 14.1. Statistics on per capita consumption of sweeteners, fat, 188 and protein 14.2. Important metabolic consequences of fructose versus glucose 193 14.3. Features of metabolic syndrome 194 B.1. Common fatty acids, their sources, and their melting points 220 B.2. Fatty acid composition of common dietary fats and oils 221 D.1. Composition of lipoproteins found in human blood 226 D.2. Classifi cation of lipoproteins by ultracentrifugation characteristics 227 D.3. Human apolipoproteins and the lipoproteins with which 227 they are associated ix
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