Iron Metabolism: From Molecular Mechanisms to Clinical Consequences (4th Revised edition)

Iron Metabolism: From Molecular Mechanisms to Clinical Consequences (4th Revised edition)

By: Robert Crichton (author)Hardback

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Description

Iron is indispensable for the growth, development and well-being of almost all living organisms. Biological systems from bacteria, fungi and plants to humans have evolved systems for the uptake, utilisation, storage and homeostasis of iron. Its importance for microbial growth makes its uptake systems a natural target for pathogenic microorganisms and parasites. Uniquely, humans suffer from both iron deficiency and iron overload, while the capacity of iron to generate highly reactive free radicals, causing oxidative stress, is associated with a wide range of human pathologies, including many neurodegenerative diseases. Whereas some essential metal ions like copper and zinc are closely linked with iron metabolism, toxic metals like aluminium and cadmium can interfere with iron metabolism. Finally, iron metabolism and homeostasis are key targets for the development of new drugs for human health. The 4th edition of Iron Metabolism is written in a lively style by one of the leaders in the field, presented in colour and covers the latest discoveries in this exciting area. It will be essential reading for researchers and students in biochemistry, molecular biology, microbiology, cell biology, nutrition and medical sciences. Other interested groups include biological inorganic chemists with an interest in iron metabolism, health professionals with an interest in diseases of iron metabolism, or of diseases in which iron uptake systems are involved (eg. microbial and fungal infections, cancer, neurodegenerative disorders), and researchers in the pharmaceutical industry interested in developing novel drugs targeting iron metabolism/homeostasis.

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Contents

Preface xii 1 Solution Chemistry of Iron 1 1.1 Iron Chemistry 1 1.2 Interactions of Iron with Dioxygen and Chemistry of Oxygen Free Radicals 2 1.3 Hydrolysis of Iron Salts 5 1.4 Formation and Characterisation of Ferrihydrite 7 1.5 Ageing of Amorphous Ferrihydrite to more Crystalline Products 10 1.6 Biomineralisation 11 1.7 Magnetite Biomineralisation by Magnetotactic Bacteria 13 1.7.1 Biogenesis of the Magnetosome Membrane 15 1.7.2 Protein Sorting 15 1.7.3 Chain Formation 16 1.7.4 Biomineralisation 16 1.7.5 A Model for Magnetosome Formation 17 References 18 2 The Essential Role of Iron in Biology 22 2.1 Introduction: Iron an Essential Element in Biology 22 2.2 Physical Techniques for the Study of Iron in Biological Systems 25 2.3 Classes of Iron Proteins 29 2.4 Haemoproteins 29 2.4.1 Oxygen Carriers 30 2.4.2 Activators of Molecular Oxygen 34 2.4.3 Electron Transport Proteins 38 2.5 Iron Sulphur Proteins 41 2.6 Non ]haem, Non ]Fe S Proteins 48 2.6.1 Mononuclear Non ]haem Iron Enzymes 48 2.6.1.1 Extradiol ]cleaving Catechol Dioxygenases 49 2.6.1.2 Rieske Oxygenases 49 2.6.1.3 ]Ketoglutarate ]dependent Enzymes 52 2.6.1.4 Pterin ]dependent Hydroxylases 54 2.6.1.5 Miscellaneous Enzymes 55 2.6.2 Dinuclear Non ]haem Iron Proteins 55 2.6.3 Proteins of Iron Storage, Transport and Metabolism 61 2.7 The Dark Side of Iron: Ros , Rns and Ntbi 62 2.7.1 ROS and RNS 63 2.7.2 NTBI and LPI 64 References 64 3 Microbial Iron Uptake 71 3.1 Introduction 71 3.2 Iron Uptake from Siderophores 74 3.2.1 Siderophores 74 3.2.2 Iron Transport across the Outer Membrane in Gram ]negative Bacteria 78 3.2.3 Transport across the Periplasm and Cytoplasmic Membrane in Gram ]negative Bacteria 86 3.2.4 Iron Uptake by Gram ]positive Bacteria 92 3.3 Fe2+ Transport Systems 93 3.4 Iron Release from Siderophores in the Cytoplasm 97 3.5 Intracellular Iron Metabolism 98 3.6 Control of Gene Expression by Iron 101 References 108 4 Iron Acquisition by Pathogens 120 4.1 Introduction 120 4.2 Host Defence Mechanisms, Nutritional Immunity 121 4.3 Pathogenicity and PAIs 123 4.4 Pathogen ]specific Iron Uptake Systems 125 4.4.1 Siderophores Associated with Virulence 125 4.4.2 Transferrin/lactoferrin Iron Uptake 126 4.4.3 Haem Iron Uptake 133 4.4.4 Ferrous Iron Uptake 138 4.4.5 Ferric Citrate Uptake by Bacillus cereus 141 4.5 Role of Fur and Fur Homologues in Virulence 141 4.6 Role of Pathogen Ecf Sigma Factors 141 4.7 Fungal Pathogens 143 References 146 5 Iron Uptake by Plants and Fungi 155 5.1 Iron Uptake by Plants 155 5.1.1 Introduction 155 5.1.2 Genome Sequencing 157 5.1.2.1 Quantitative Trait Loci 158 5.1.3 Iron Acquisition by the Roots of Plants 160 5.1.3.1 Non ]graminaceous Plants 161 5.1.3.2 Graminaceous Plants 164 5.1.4 Long ]distance Iron Transport 166 5.2 Iron Metabolism and Homeostasis in Plants 169 5.2.1 New Tools in Plant Research 169 5.2.2 Intracellular Iron Metabolism 170 5.2.3 Plant Iron Homeostasis 171 5.2.4 Diurnal Regulation of Iron Homeostasis 176 5.3 Iron Uptake, Metabolism and Homeostasis in Fungi 178 5.3.1 Introduction 178 5.3.2 High ] and Low ]affinity Iron Uptake Pathways 179 5.3.3 Siderophore ]mediated Iron Uptake 184 5.3.4 Intracellular Iron Metabolism 185 5.3.5 Iron Homeostasis 186 References 190 6 Cellular Iron Uptake and Export in Mammals 205 6.1 The Transferrins 205 6.1.1 Introduction 205 6.1.2 The Transferrin Family 206 6.1.3 Structure of Transferrins 211 6.1.4 Transferrin iron Binding 215 6.1.5 Binding of other Metals by Transferrin 218 6.2 Cellular Iron Uptake 219 6.2.1 The Transferrin Receptors 219 6.2.2 The Transferrin to Cell Cycle and Iron Release 222 6.2.3 Iron Uptake from other Sources 228 6.3 Cellular Iron Export 230 References 236 7 Mammalian Iron Metabolism and Dietary Iron Absorption 247 7.1 An overview of Mammalian Iron Metabolism 247 7.1.1 Introduction 247 7.1.2 The Way Different Cells Handle Iron 249 7.2 Mammalian Iron Absorption 251 7.2.1 Introduction 251 7.2.2 The Intestinal Mucosa 252 7.2.3 Sources of Dietary Iron 253 7.2.4 Iron Loss and Effects on Uptake 255 7.3 Molecular Mechanisms of Mucosal Iron Absorption 256 7.3.1 Iron Uptake at the Apical Pole 256 7.3.2 Iron Transit through and Storage in Enterocytes 259 7.3.3 Iron Efflux across the Basolateral Membrane 259 7.3.4 Regulation of Iron Uptake by the Enterocyte 261 References 261 8 Intracellular Iron Utilisation 265 8.1 Intracellular Iron Pools 265 8.1.1 Introduction 265 8.1.2 The Cytosolic Labile Iron Pool (LIP) 266 8.1.3 Distribution of Iron in the Cytosol 268 8.1.4 Other Intracellular Iron Pools 269 8.2 Mitochondrial Iron Metabolism 271 8.2.1 Mitochondrial Iron Uptake and Storage 271 8.2.2 Mitochondrial Fe S Protein Biogenesis 271 8.2.3 Maturation of Cytosolic and Nuclear Fe S Proteins 275 8.2.4 Haem Biosynthesis 283 8.3 Haem Oxygenase 287 8.3.1 Structure and Catalytic Cycle 287 8.3.2 Activation of Haem Oxygenase 1 (HO ]1) 292 References 292 9 Iron Storage Proteins 300 9.1 Introduction 300 9.2 The Ferritin Superfamily and Haemosiderins 301 9.2.1 The Ferritin Superfamily 301 9.2.2 Structure of Vertebrate and Invertebrate Ferritins 304 9.2.3 Plant and Bacterial Ferritins 308 9.2.4 Dps Proteins and Rubrerythrins 313 9.2.5 The Mineral Core 319 9.2.6 Haemosiderins 319 9.3 Iron Uptake and Release from Ferritin 320 9.3.1 Iron Uptake in Ferritins 320 9.3.1.1 Entry of Fe(II) into the Protein Shell 321 9.3.1.2 Oxidation of Fe2+ by Ferroxidase Sites 323 9.3.1.3 Mineralisation of the Iron Core 325 9.3.2 Iron Uptake in Dps Proteins 333 9.3.3 Iron Release from Ferritin 333 9.4 Biotechnological Applications of Ferritins 335 References 336 10 Cellular and Systemic Iron Homeostasis 346 10.1 Cellular Iron Homeostasis 346 10.1.1 Translational Control of Protein Synthesis 346 10.1.2 The IRE/IRP System 347 10.1.3 The IREs distribution and Structure 348 10.1.4 Structural Features of IRP1 and 2 351 10.1.5 The IRE/IRP System Revisited Iron Controls Iron 353 10.1.6 Metabolic Consequences of Mutations in Ires 357 10.2 Systemic Iron Homeostasis 357 10.2.1 Introduction 357 10.2.2 Hepcidin, the Key Player 358 10.2.3 Factors which Regulate Hepcidin Synthesis 360 10.2.3.1 Iron Availability 361 10.2.3.2 Inflammatory Stimuli 364 10.2.3.3 Erythropoietic Demand 364 10.2.3.4 Hypoxia 365 10.2.3.5 Endocrine Signals 366 10.3 Integration of Iron Homeostatic Systems 367 References 367 11 Iron Deficiency, Iron Overload and Therapy 376 11.1 Iron ]deficiency Anaemia (Ida) 376 11.1.1 Introduction The Size of the Problem 376 11.1.2 Causes of Ida 378 11.1.3 Clinical Stages and Diagnosis of Ida 380 11.1.4 Therapeutic Approaches 383 11.1.5 Anaemia of Chronic Disease (Acd ), Iron Refractory Ida (Irida ) and Anaemia of Chronic Kidney Disease (Ckd) 384 11.2 Hereditary Iron Overload 386 11.2.1 Introduction 386 11.2.2 Hereditary Haemochromatosis (Hh) 386 11.2.3 Causes of HH 387 11.2.4 Types of Haemochromatosis 388 11.2.4.1 Hfe ]related (Type 1) Haemochromatosis 388 11.2.4.2 Juvenile (Type 2) Haemochromatosis 390 11.2.4.3 Tfr2 ]related (Type 3) Haemochromatosis 390 11.2.4.4 Ferroportin Disease 390 11.2.5 Therapy of Hereditary Haemochromatosis 391 11.3 Acquired Iron Overload 395 11.3.1 Introduction Causes of Acquired Iron Overload 395 11.3.2 Mechanisms of Iron Toxicity 397 11.3.3 Evaluation of Iron Overload 398 11.3.4 Chelation Therapy for Acquired Iron Overload 400 11.3.5 Other Therapeutic Approaches 405 References 406 12 Iron and Immunity 418 12.1 Introduction 418 12.1.1 Innate Immunity 419 12.2 The Key Role of Macrophages 422 12.2.1 Overview 422 12.2.2 Macrophage Phenotypes 425 12.2.3 Microglia 426 12.3 Effect of Iron Status on Phagocytic Cell Function 429 12.3.1 Iron Deficiency 429 12.3.2 Iron Overload 430 12.4 Effect of Phagocytic Cell Function on Iron Metabolism 431 12.4.1 The IRE Iron Regulatory Protein (IRP) System 431 12.5 Effector Molecules of the Innate Immune System 433 12.5.1 Toll ]like Receptors 433 12.5.2 NF ] B 433 12.5.3 Hypoxia ]Inducible Factor 1 (Hif 1) 434 12.5.4 Haem Oxygenase 435 12.5.5 DMT1, Nramp1 437 12.6 Adaptive Immunity 437 12.6.1 Cd8+ Lymphocytes and Cytotoxicity 438 12.6.2 CD4+ lymphocytes 438 12.7 Immune Function and other Factors 438 12.7.1 Iron Supplementation and Immune Function 438 12.7.2 Immune Function in the Elderly Population 439 12.7.3 Iron Overload and Immune Function 439 12.7.4 Thalassaemia 440 12.8 Concluding Remarks 440 References 440 13 Iron and Oxidative Stress 444 13.1 Oxidative stress 444 13.1.1 Introduction Milestones in the History of Life 444 13.1.2 Reactive Oxygen Species (Ros ) and Reactive Nitrogen Species (Rns) 447 13.1.3 Cellular Defence Mechanisms Against Oxidative Stress 450 13.1.4 Role of ROS and RNS in Cell Signalling 460 13.1.5 ROS, RNS and Oxidative Damage 466 References 476 14 Interactions between Iron and other Metals 482 14.1 Introduction 482 14.2 Iron Interactions with Essential Metals 483 14.2.1 Copper 483 14.2.1.1 Introduction 483 14.2.1.2 Copper Acquisition and Metabolism 485 14.2.1.3 Copper Chaperones 486 14.2.1.4 Iron copper Interactions 487 14.2.2 Zinc 494 14.2.2.1 Introduction 494 14.2.2.2 Iron zinc Interactions 496 14.2.3 Cobalt 497 14.2.3.1 Introduction 497 14.2.3.2 Iron cobalt Interactions 498 14.2.4 Manganese 500 14.2.4.1 Iron manganese Interactions 500 14.2.5 Calcium 501 14.2.5.1 Iron calcium Interactions 501 14.3 Iron Interactions with Toxic Metals 502 14.3.1 Lead 502 14.3.2 Cadmium 503 14.3.3 Aluminium 505 References 507 15 Iron Homeostasis and Neurodegeneration 516 15.1 Introduction 516 15.2 Brain iron 517 15.2.1 Brain Iron Homeostasis 517 15.2.2 Aging and Brain Iron Content 518 15.3 Iron and Neurodegeneration 522 15.3.1 Introduction 522 15.3.2 Adverse Effects of Iron in Neurodegeneration 522 15.3.2.1 Toxicity of ROS and RNS 522 15.3.2.2 Iron and Mitochondrial Function 523 15.3.2.3 Protein Aggregation 523 15.4 Neurodegeneration with Brain Iron Accumulation 524 15.4.1 Aceruloplasminaemia 524 15.4.2 Neuroferritinopathy 526 15.4.3 Other NBIAs 528 15.5 Other Monogenic Neurodegenerative Diseases 530 15.5.1 Huntington s Disease 530 15.5.2 Friedreich s Ataxia 532 15.6 Neurodegeneration Involving Multiple Genes 533 15.6.1 Parkinson s Disease (PD) 533 15.6.2 Alzheimer s Disease (AD) 535 15.6.3 Multiple Sclerosis (MS) 537 15.7 Intracerebral Haemorrhage 538 References 539 Concluding Remarks 544 Index 547

Product Details

  • publication date: 27/05/2016
  • ISBN13: 9781118925614
  • Format: Hardback
  • Number Of Pages: 576
  • ID: 9781118925614
  • weight: 1350
  • ISBN10: 1118925610
  • edition: 4th Revised edition

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