Iron Metabolism : From Molecular Mechanisms to Clinical Consequences

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ISBN: 9780470010280 | 0470010282
Cover: Hardcover
Copyright: 5/26/2009

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Iron is of fundamental importance to the growth, development and well-being of almost all living organisms. Multiple biological systems have evolved for the uptake, utilisation, storage, and homeostasis of iron in microbes, plants and mammals. Both iron deficiency and iron overload are found extensively in humans; the intimate links between iron and oxidative stress are associated with a wide range of pathologies. Iron has a well established role in infections by a range of microorganisms and parasites. Other metals such as copper and zinc are also closely linked with iron metabolism. Iron overloads and deficiencies are important factors in the health of humans and are therefore a key target in drug development.Iron Metabolism: From Molecular Mechanisms to Clinical Consequences, 3rd Edition presents a comprehensive overview of this important field.Topics covered include:Solution chemistry of iron in biological media The importance of iron for biological systems Microbial iron transport and metabolism Iron uptake by plants and fungi Cellular iron uptake and export in mammals Intracellular iron storage and biomineralization Intracellular iron metabolism and cellular iron homeostasis Iron absorption in mammals, with particular reference to man, and regulation of systemic iron balance Pathophysiology of iron deficiency and iron overload in man Iron and oxidative stress Brain iron homeostasis and its perturbation in various neurodegenerative diseases Interactions between iron and other metalsWritten in a lively style by one of the leaders in the field and presented in full colour, this third, expanded edition of Iron Metabolism has been fully updated with the latest discoveries. Major additions include recent information on mitochondrial iron metabolism and the role of frataxin; transcriptional control of iron homeostasis; orally active iron chelators; the roles of hepcidin and erythropoietin; the increasing number of types of iron overload; and the importance of iron in Alzheimer's disease.Iron Metabolism is essential reading for researchers and students in biochemistry, molecular biology, microbiology, cell biology, nutrition and the medical sciences. It will also find space on the bookshelves of bioinorganic chemists with an interest in iron metabolism, health professionals with an interest in diseases of iron metabolism, and pharmacologists in the pharmaceutical industry interested in developing novel iron-binding drugs.

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Preface	p. xi
Solution Chemistry of Iron in Biological Media	p. 1
Aqueous Solution Chemistry of Iron	p. 1
Oxygen Free Radicals	p. 2
Iron Hydrolysis - a Ubiquitous Phenomenon	p. 5
Hydrolysis of Iron(III) in Acid Media - Formation of Polynuclear Species	p. 7
Ageing of Amorphous Ferrihydrite to more Crystalline Products	p. 9
Biomineralisation	p. 10
Magnetite Biomineralisation by Magnetotactic Bacteria	p. 12
References	p. 15
The Importance of Iron for Biological Systems	p. 17
Introduction	p. 17
Physical Techniques for the Study of Iron in Biological Systems	p. 19
Haemoproteins	p. 24
Oxygen Carriers	p. 24
Activators of Molecular Oxygen	p. 28
Electron Transport Proteins	p. 35
Iron-Sulfur Proteins	p. 39
Other Iron Containing Proteins	p. 45
Mononuclear Non-Haem Iron Enzymes	p. 45
Dinuclear Non-Haem Iron Enzymes	p. 50
References	p. 56
Microbial Iron Transport and Metabolism	p. 59
Introduction	p. 59
Siderophores	p. 63
Iron Transport Across the Outer Membrane in Gram-Negative Bacteria	p. 66
Transport Across the Periplasm and Cytoplasmic Membrane	p. 75
Iron Release from Ferric Siderophores and Ferric Reduction	p. 79
Fe2+ Transport Systems in E. coli	p. 80
Fe3+ Iron Acquisition by Pathogens	p. 80
Intracellular Iron Metabolism	p. 86
Control of Gene Expression by Iron	p. 88
References	p. 94
Iron Uptake by Plants and Fungi	p. 103
Iron Acquisition by Plants	p. 103
Introduction	p. 103
Iron Acquisition by the Roots of Plants	p. 105
Long Distance Iron Transport	p. 110
Intracellular Iron Transport	p. 112
Iron Acquisition by Yeast	p. 118
Introduction - Pathways for Iron Uptake	p. 118
Cell Surface Reductases	p. 119
High Affinity Iron Transport System	p. 120
Low Affinity Ferrous Iron Transport	p. 125
Siderophore-Mediated Iron Uptake	p. 126
Intracellular Iron Metabolism	p. 129
Iron Transport in Other Fungi	p. 130
Regulation of Iron Uptake/Homeostasis in Yeast	p. 131
References	p. 131
Cellular Iron Uptake and Export in Mammals	p. 141
The Transferrins	p. 141
Structure of Transferrins	p. 143
Transferrin Iron Binding and Release	p. 146
Iron Uptake by Mammalian Cells - Uptake of Transferrin Bound Iron	p. 151
The Transferrin Receptor	p. 151
The Transferrin-to-Cell Cycle	p. 155
Transferrin Binding to its Receptor	p. 157
Cellular Iron Uptake and Export	p. 161
Red Blood Cell Precursors	p. 162
Tissue Macrophages	p. 164
Hepatocytes	p. 167
Uptake of Iron from Other Sources than Transferrin	p. 168
Nontransferrin Bound Iron	p. 169
Ferritin Bound Iron	p. 170
Haptoglobin and Haemopexin as Iron Transporters	p. 170
References	p. 173
Intracellular Iron Storage and Biomineralisation	p. 183
Intracellular Iron Storage	p. 183
Ferritin: Distribution and Primary Structure	p. 184
Three-Dimensional Structure	p. 186
The Mineral Core	p. 198
Iron Deposition in Ferritin	p. 200
Iron Mobilisation from Ferritin	p. 207
Haemosiderin	p. 209
Biomineralisation	p. 210
References	p. 215
Intracellular Iron Metabolism and Cellular Iron Homeostasis	p. 223
Intracellular Iron Metabolism	p. 223
The Labile Iron Pool	p. 224
Mitochondrial Iron Uptake and Metabolism	p. 226
Haem Biosynthesis	p. 228
Iron-Sulfur Protein Biogenesis in Eukaryotes	p. 233
Intracellular Haem Degradation - Haem Oxygenase	p. 240
Cellular Iron Homeostasis	p. 247
Structural Features of IREs	p. 251
Hereditary Hyperferritinaemia Cataract Syndrome	p. 253
Iron Regulatory Protein 1	p. 254
Iron Regulatory Protein 2	p. 259
References	p. 261
Iron Absorption in Mammals, with Particular References to Man, and Regulation of Systemic Iron Balance	p. 271
Iron Metabolism in Man: An Overview	p. 271
Sources of Dietary Iron in Man and the Importance of Luminal Factors	p. 273
Iron Losses and Requirements for Absorbed Iron	p. 275
Molecular Mechanisms of Mucosal Iron Absorption	p. 276
Iron Uptake at the Apical Pole	p. 279
Iron Transfer Across the Mucosal Cell	p. 282
Release of Iron at the Basolateral Membrane and Uptake by Apotransferrin	p. 283
Regulation of Iron Uptake by the Enterocyte	p. 284
Regulation of Systemic Iron Balance	p. 285
References	p. 294
Pathophysiology of Iron Deficiency and Iron Overload in Man	p. 299
Introduction: Acquired and Genetic Disorders of Iron Metabolism	p. 299
Homeostatic Control of the Internal Milieu and Consequences of Its Disruption	p. 300
Iron Overload Syndromes	p. 303
Primary Iron Overload, Hereditary Haemochromatosis (HH)	p. 303
HFE Haemochromatosis (Type 1)	p. 304
Other Types of Haemochromatosis	p. 308
Nonhaemochromatotic Primary Iron Overload	p. 311
Treatment of Primary Iron Overload	p. 312
Secondary Iron Overload	p. 313
Treatment of Secondary Iron Overload	p. 315
Iron Deficiency and IDA	p. 318
Epidemiology	p. 318
Causes	p. 319
Clinical Stages of Iron Deficiency and Laboratory Diagnosis	p. 320
Treatment of Iron Deficiency	p. 322
Anaemia of Chronic Disease	p. 324
Conclusions	p. 324
References	p. 325
Iron and Oxidative Stress	p. 335
Introduction to Free Radicals	p. 335
Reactive Oxygen Species (ROS)	p. 336
Cytoprotective Enzymes and Antioxidants	p. 338
Superoxide Dismutase	p. 338
Catalase and Glutathione Peroxidase	p. 340
Glutathione	p. 340
Thioredoxin System	p. 342
Haem Oxygenase	p. 342
Ferritin	p. 342
Low Molecular Weight Antioxidants	p. 343
Ageing and Cytoprotection	p. 345
Oxidative Stress	p. 348
NFkB	p. 348
Caspases	p. 350
JNK	p. 353
MAPK Signalling Pathway-amplification Cascade	p. 353
Cyclin Dependent Kinases	p. 356
Deregulation of Calcium Homeostasis and Oxidative Stress	p. 357
Nitric Oxide and Cyclic Guaylate Cyclase	p. 358
Activation of cAMP Dependent PKA	p. 360
Importance of Iron, ROS and RNS in Phagocytic Cells	p. 360
Macrophages	p. 360
Glial Cells	p. 364
References	p. 365
Brain Iron Homeostasis and Its Perturbation in Various Neurodegenerative Diseases	p. 371
Introduction	p. 371
Mechanisms for Iron Transport into Brain	p. 372
Importance of Iron in the Developing Foetus	p. 376
Iron Uptake and Turnover Within the Brain	p. 377
Importance of IRPs in Brain Iron Homeostasis	p. 378
Brain Iron Speciation	p. 379
Neurodegenerative Diseases	p. 379
Parkinson's Disease	p. 381
Alzheimer's Disease	p. 389
Frederich's Ataxia	p. 393
Aceruloplasminaemia	p. 395
References	p. 398
Interactions Between Iron and Other Metals	p. 403
Introduction	p. 403
Interactions Between Iron and Essential Metals	p. 404
Mars and Venus - Iron and Copper	p. 404
Iron and Zinc	p. 414
Iron and Manganese	p. 420
Iron and Cobalt	p. 424
Iron and Toxic Metals	p. 429
Iron and Aluminium	p. 429
Iron and Lead	p. 432
Iron and Cadmium	p. 434
References	p. 435
Concluding Remarks	p. 445
Index	p. 453
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Iron Metabolism : From Molecular Mechanisms to Clinical Consequences

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