Lipid Biochemistry: For Medical Sciences

By Ashour Saleh Eljamil

Lipid biochemistry can seem overwhelming, which is why it needs to be explained in a simple and straightforward manner.

Ashour Saleh Eljamil, a renowned professor of biochemistry, has written this textbook for undergraduate students in the medical sciences, but its a resource that anyone can use to bolster their knowledge about this important subject.

To fully understand biochemistry, you need to know how biomolecules are structured, which is why the first chapter emphasizes the individual chemical structure of various lipid classes. Youll also learn how dietary lipids are digested and absorbed as well as how their metabolism works in separate chapters focusing on fatty acids synthesis, fatty acid oxidation, acylglycerols and sphingolipids, glycolipids, cholesterol, plasma lipoproteins, steroid hormones, and fat-soluble vitamins.

While scientists have studied lipid biochemistry for three centuries, its only in the past few decades that weve begun to understand why its so important. Gain a clearer understanding of the world with insights about bile acids, sterols, carotenoids, sex hormones, vitamin K and much, much more when you dive into the world of Lipid Biochemistry.

• Language: English
• Publisher: iUniverse
• Release date: Mar 30, 2015
• ISBN: 9781491742228

Ashour Saleh Eljamil

Ashour Saleh Eljamil, a native of Tripoli, Libya, earned a doctorate in biochemistry from University College Dublin. In 1989 he joined the biochemistry staff at the Faculty of Medicine, Tripoli University and has worked with the biochemistry units at the medical laboratories of Salahudeen Hospital and Tripoli Medical Centre.

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LIPID BIOCHEMISTRY

Copyright © 2015 Ashour Saleh Eljamil.

All rights reserved. No part of this book may be used or reproduced by any means, graphic, electronic, or mechanical, including photocopying, recording, taping or by any information storage retrieval system without the written permission of the publisher except in the case of brief quotations embodied in critical articles and reviews.

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ISBN: 978-1-4917-4223-5 (sc)

ISBN: 978-1-4917-4222-8 (e)

Library of Congress Control Number: 2014917826

iUniverse rev. date: 03/30/2015

CONTENTS

Foreword

Preface

Acknowledgements

Chapter 1: Lipid Chemistry

Introduction

Functions Of Lipids

Classification Of Lipids

1) Fatty Acyl (FA)

Nomenclature

Saturated fatty acids

Branched-chain fatty acids

Unsaturated fatty acids

Monounsaturated fatty acids

Polyunsaturated fatty acids (PUFAs)

Essential fatty acids (EFAs)

Eicosanoids

2) Glycerolipids (GL)

3) Glycerophospholipids (GP)

Cardiolipin

Plasmalogens

Major functions of glycerophospholipids (GPs)

4) Sphingolipids (SPs)

Sphingoid bases

Ceramides

Sphingomyelins

Glycosphingolipids

Neutral glycosphingolipids

Acidic glycosphingolipids

Gangliosides

Sulphatides (sulphoglycosphingolipids)

Major functions of sphingolipids

5) Sterol Lipids (SLs)

Cholesterol

Functions of cholesterol

Steroids

Steroid hormone nomenclature

Secosteroids

Bile acids

Steroid conjugates

6) Prenol Lipids (PRs)

7) Saccharolipids (SLs)

8) Polyketides (PKs)

Lipid Peroxidation

Antioxidants

Separation And Identification Of Lipids

Conclusion

Selected Readings

Chapter 2: Digestion And Absorption Of Dietary Lipids

Introduction

Digestion Of Lipids In The Mouth And Stomach

Emulsification Of Dietary Lipids

Hormonal Control Of Lipid Digestion

Degradation Of Dietary Lipids

Triacylglycerol (TAG)

Cholesterol ester (CE)

Phospholipids

Absorption Of Dietary Lipids

Formation Of Chylomicrons (CMs)

Abetalipoproteinemia

Lipid Malabsorption (Steatorrhea)

Conclusion

Selected Readings

Chapter 3: Synthesis Of Fatty Acids

Introduction

De Novo Synthesis Of Fatty Acids

Sources of acetyl-CoA

Sources of NADPH

Steps Of Lipogenesis

1. Formation of malonyl-CoA

2. Production of palmitate

Regulation of lipogenesis

Fate of palmitate

The Microsomal System For Chain Elongation

The Mitochondrial System For Chain Elongation

Biosynthesis Of Monounsaturated Fatty Acids

Biosynthesis Of Polyunsaturated Fatty Acids (PUFAs)

Conversion of linoleate to arachidonate

Biosynthesis Of Eicosanoids

The cyclooxygenase pathway

Inhibition of prostanoid synthesis

The lipoxygenase pathway

Biological functions of eicosanoids

Conclusion

Selected Readings

Chapter 4: Oxidation Of Fatty Acids

Introduction

Lipolysis

Regulation of lipolysis

Fate of glycerol

Pathways Of Fatty Acid Oxidation

ß-Oxidation

Activation of fatty acids

Role of carnitine in fatty-acid oxidation

Carnitine deficiency

Carnitine palmitoyltransferase (CPT) deficiency

Reactions of ß-oxidation

Energetics

Oxidation of fatty acids with an odd number of carbon atoms

Oxidation of unsaturated fatty acids

α-Oxidation

ω-Oxidation

Peroxisomal ß-oxidation

Diseases Resulting From Impaired Oxidation Of Fatty Acids

Jamaican vomiting sickness

Dicarboxylic aciduria

Zellweger’s syndrome

X-linked adrenoleukodystrophy (ALD)

Ketone-Body Synthesis (Ketogenesis)

Use of ketone bodies

Conclusion

Selected Readings

Chapter 5: Metabolism Of Acylglycerols And Sphingolipids

Introduction

Metabolism Of Acylglycerols

Biosynthesis Of Phosphatidate

Biosynthesis Of Triacylglycerols (TAG)

Biosynthesis Of Glycerophospholipids

Biosynthesis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE)

Biosynthesis of phosphoinositides

Biosynthesis of cardiolipin

Biosynthesis Of Ether Phospholipids

Degradation Of Glycerophospholipids

Biosynthesis Of Sphingolipids

Conclusion

Selected Readings

Chapter 6: Metabolism Of Glycosphingolipids

Introduction

Biosynthesis Of Glycosphingolipids

Glucosylceramide (Glc-Cer) And Galactosylceramide (Gal-Cer) Formation

Lactosylceramide Production

Ganglioside Synthesis

Degradation Of Glycosphingolipids

Lipid-Storage Diseases

Treatment Of Sphingolipidoses

Conclusion

Selected Readings

Chapter 7: Metabolism Of Cholesterol

Introduction

Biosynthesis Of Cholesterol

1. Formation of mevalonate

2. Formation of squalene

3. Conversion of squalene to cholesterol

Regulation Of Hmg-Coa Reductase

Degradation Of Cholesterol

Synthesis Of Bile Acids

Enterohepatic Circulation

Cholelithiasis

Conclusion

Selected Readings

Chapter 8: Metabolism Of Lipoproteins

Introduction

Types Of Lipoprotein

Metabolism Of Chylomicrons

Formation Of Chylomicrons

Metabolism Of Very-Low-Density Lipoprotein (VLDL)

Metabolism Of Low-Density Lipoprotein (LDL)

Metabolism Of High-Density Lipoprotein (HDL)

Fatty Liver

Nonalcoholic fatty liver disease (NAFLD)

Alcoholism

Cholesterol And Cardiovascular Disease

Reduction Of Plasma Cholesterol Concentration By Change Of Diet

Abnormal Lipoproteins

Lipoprotein (a) [LP(a)]

ß-Very-low-density lipoprotein (ß-VLDL)

Lipoprotein-X (LP-X)

Diseases Of Lipoprotein Metabolism

Hypolipoproteinemia

Abetalipoproteinemia

Familial hypobetalipoproteinemia

Tangier disease (familial alpha-lipoprotein deficiency)

Hyperlipoproteinemia (hyperlipidemia)

Hyperlipidemia type I

Hyperlipidemia type II (familial hypercholesterolemia)

Hyperlipidemia type III

Hyperlipidemia type IV

Hyperlipidemia type V

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency

Conclusion

Selected Readings

Chapter 9: Metabolism Of Steroid Hormones

Introduction

Major Functions Of Steroid Hormones

Biosynthesis Of Steroid Hormones

Biosynthesis Of Adrenal Cortical Steroid Hormones

Biosynthesis Of Sex Hormones

Male sex hormones (androgens)

Female sex hormones (estrogens, progestins)

Transport Of Steroid Hormones

Corticosteroid-binding globulin (CBG)

Sex-hormone-binding globulin (SHBG)

Androgen-binding protein (ABP)

Mechanism Of Steroid Hormone Action

Excretion Of Steroid Hormones

Abnormalities In Steroid Hormone Secretion

Hypoadrenocorticism

Congenital adrenal hyperplasia (CAH)

Addison’s disease (primary adrenal insufficiency)

Cushing’s syndrome

Androgen insensitivity syndrome (AIS)

5α-reductase-2 deficiency

Male hypogonadism

Female hypogonadism

Conclusion

Selected Readings

Chapter 10: Fat-Soluble Vitamins

Introduction

Vitamin A (Retinol)

Provitamin A (ß-carotene)

Digestion and absorption of vitamin A

Storage, release, and transport

Functions of vitamin A

Visual cycle

Reproduction

Dietary sources of vitamin A

Vitamin A toxicity (hypervitaminosis A)

Vitamin A deficiency

Vitamin D

Formation of vitamin D

Formation of 1,25-dihydroxycholecalciferol (calcitriol)

Biological functions of vitamin D

Deficiency of vitamin D

Vitamin D toxicity

Vitamin E (Tocopherol)

Sources and requirements of vitamin E

Deficiency of vitamin E

Functions of vitamin E

Antioxidant functions

Non-antioxidant functions

Infertility

Vitamin K

Dietary sources and requirements of vitamin K

Biological functions of vitamin K

Vitamin K deficiency

Conclusion

Selected Readings

Abbreviations

Glossary

With love and respect to my wife, Miriam; my son, Mohamed; and my daughters, Esra, Abbrar, and Ala; and to the spirit of my dearest daughter, Aya.

Ashour Saleh Eljamil, 2015

FOREWORD

Current knowledge and understanding of lipid biochemistry has evolved rapidly in recent decades. This has happened because prior to recent decades, lipids were not a popular area of study except by hardy chemists who did not mind working with large volumes of flammable and often toxic organic solvents (such as methanol, chloroform, and ether) and for whom the methods of fractionation commonly used with water-soluble compounds such as proteins and carbohydrates were not suitable. However, the development of a wide variety of chromatographic methods in the second half of the last century opened up the subject for the study of the wide diversity of lipids of human and animal origin. This has made it possible to move from the study of adipose tissue, which consists mostly of triacylglycerols (which are storage lipids) to that of other tissues in which the lipids are mostly polar and structural in function (such as phospholipids, sphingolipids, cerebrosides, and gangliosides). The combination of gas-liquid chromatography and mass spectrometry played a key role in this amazing growth.

It is not common knowledge that the non-water components (i.e. about 35%) of the theoretical 70 kg male human body consist of approximately equal amounts of lipid (about 13%, or 9 kg) and protein (about 15%, or 11 kg) and the rest of skeletal and other minerals, carbohydrates, and nucleic acids. In severe obesity, the lipid content can account for up to about 70% (or 57 kg) of body weight, mostly in subcutaneous adipose tissue. The ease with which extra groceries are converted into storage fat contrasts sharply with the difficulty that many obese individuals have in getting rid of their excess store of fat.

Readers of this book are likely to be more interested in its factual contents than in the history of their acquisition. This is natural and understandable but may lead readers to form the impression that these are the products of recent decades only. This would be unfair to the many inventive pioneers who prepared the grounds for much of our recent knowledge. Among these were William Prout, the English physician, and Claude Bernard, the illustrious French physiologist. In 1827, the former classified the organic components of human diet into saccharine, oily, and albuminous, or, in more modern terminology, carbohydrate, lipid, and protein. Between 1846 and 1856, the latter demonstrated the lipase activity of the rabbit pancreas, showing that pancreatic juice breaks down fat into glycerol and fatty acids and that pancreatic juice and bile are essential for the digestion and absorption of fat in the duodenum. Unsophisticated their methods may have been, but very significant and enduring were their conclusions.

The proteins are encoded by the bulk of the genes in DNA and provide the machinery for the production of body lipids from the groceries we consume. This machinery consists of enzymes, carriers, hormones, agents for gene regulation, and such. Elucidation of what it is that the different structural lipids specifically do in the membrane systems of the body cells, especially those of the central nervous system, is a gigantic task that awaits future research. Although they are not direct gene products, the lipids deserve our attention and admiration.

This book is characterized by its comprehensive survey of the subject, the brevity of its descriptions, and its primary interest in making the subject relevant to readers interested in the molecular aspects of the working of their bodies. It is a valuable guide to the second-largest component of the non-obese human body and to some of the medical problems that may afflict the body in its handling of this fascinating component.

Francis Vella

M.D., M.A.(Oxon), Ph.D., hon D.Sc.

Retired Professor of Biochemistry, University of Saskatchewan, Canada

PREFACE

This book introduces lipid biochemistry to undergraduate students in the medical sciences without overloading the description with unnecessary details. Understanding biochemistry requires familiarity with the structure of biomolecules, as this provides a visual presentation of their chemistry and, frequently, of their function. For this reason, the first chapter places special emphasis on the individual chemical structure of the various lipid classes. The digestion and absorption of dietary lipids is briefly discussed in the second chapter. Aspects of their metabolism is presented in separate chapters on fatty acid synthesis, fatty acid oxidation, acylglycerols and sphingolipids, glycolipids, cholesterol, plasma lipoproteins, steroid hormones, and fat-soluble vitamins.

The synthesis of saturated, monounsaturated, and polyunsaturated fatty acids and eicosanoids are described, but emphasis is given to the saturated type. The chapter dealing with the oxidation of fatty acids starts with the mobilization of stored fat, continues with the pathways of fatty-acid oxidation, and concludes with the diseases resulting from impaired oxidation of fatty acids.

Chapter 5 simply describes the biosynthesis and degradation of phospholipids (acylglycerols and sphingophospholipids).

Glycolipid metabolism