Iron Metabolism From Molecular Mechanisms to Clinical Consequences

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

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
2.5 Iron-Sulphur Proteins 41
2.6 Non-haem, Non-Fe-S Proteins 48
2.7 The Dark Side of Iron: ROS, RNS and NTBI 62

3 Microbial Iron Uptake 71
3.1 Introduction 71
3.2 Iron Uptake from Siderophores 74
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

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
4.5 Role of Fur and Fur Homologues in Virulence 141
4.6 Role of Pathogen ECF Sigma Factors 141
4.7 Fungal Pathogens 143

5 Iron Uptake by Plants and Fungi 155
5.1 Iron Uptake by Plants 155
5.2 Iron Metabolism and Homeostasis in Plants 169
5.3 Iron Uptake, Metabolism and Homeostasis in Fungi 178

6 Cellular Iron Uptake and Export in Mammals 205
6.1 The Transferrins 205
6.2 Cellular Iron Uptake 219
6.3 Cellular Iron Export 230

7 Mammalian Iron Metabolism and Dietary Iron Absorption 247
7.1 An overview of Mammalian Iron Metabolism 247
7.2 Mammalian Iron Absorption 251
7.3 Molecular Mechanisms of Mucosal Iron Absorption 256

8 Intracellular Iron Utilisation 265
8.1 Intracellular Iron Pools 265
8.2 Mitochondrial Iron Metabolism 271
8.3 Haem Oxygenase 287

9 Iron Storage Proteins 300
9.1 Introduction 300
9.2 The Ferritin Superfamily and Haemosiderins 301
9.3 Iron Uptake and Release from Ferritin 320
9.4 Biotechnological Applications of Ferritins 335

10 Cellular and Systemic Iron Homeostasis 346
10.1 Cellular Iron Homeostasis 346
10.2 Systemic Iron Homeostasis 357
10.3 Integration of Iron Homeostatic Systems 367

11 Iron Deficiency, Iron Overload and Therapy 376
11.2 Hereditary Iron Overload 386
11.3 Acquired Iron Overload 395

12 Iron and Immunity 418
12.1 Introduction 418
12.2 The Key Role of Macrophages 422
12.3 Effect of Iron Status on Phagocytic Cell Function 429
12.4 Effect of Phagocytic Cell Function on Iron Metabolism 431
12.5 Effector Molecules of the Innate Immune System 433
12.6 Adaptive Immunity 437
12.7 Immune Function and other Factors 438
12.8 Concluding Remarks 440

13 Iron and Oxidative Stress 444
13.1 Oxidative stress 444

14 Interactions between Iron and other Metals 482
14.1 Introduction 482
14.2 Iron Interactions with Essential Metals 483
14.3 Iron Interactions with Toxic Metals 502

15 Iron Homeostasis and Neurodegeneration 516
15.1 Introduction 516
15.2 Brain iron 517
15.3 Iron and Neurodegeneration 522
15.4 Neurodegeneration with Brain Iron Accumulation 524
15.5 Other Monogenic Neurodegenerative Diseases 530
15.6 Neurodegeneration Involving Multiple Genes 533
15.7 Intracerebral Haemorrhage 538

References 539
Concluding Remarks 544
Index 547