Iron Metabolism: From Molecular Mechanisms to Clinical Consequences

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. INDICE: Preface .1. Solution Chemistry of Iron .1.1 Iron chemistry .1.2 Interactions of iron with dioxygen and chemistry of oxygen free radicals .1.3 Hydrolysis of iron salts .1.4 Formation and characterization of ferrihydrite .1.5 Ageing of Amorphous Ferrihydrite to more Crystalline Products .1.6 Biomineralization .1.7 Magnetite Biomineralization by Magnetotactic Bacteria .References .2. The Essential Role of Iron in Biology .2.1 Introduction iron an essential element in biology .2.2 Physical methods for the study of iron in biological systems .2.3 Classes of iron proteins .2.4 Haemoproteins .2.4.1 O2 carriers .2.4.2 Activators of molecular O2 .2.4.3 Electron transporters .2.5 Iron–sulphur proteins .2.6 Non–haem, non–FeS proteins .2.6.1 Mononuclear non–haem iron proteins .2.6.2 Dinuclear non–haem iron proteins .2.7 Proteins of iron storage, transport and metabolism .2.8 The dark side of iron ROS, RNS and NTBI .References .3. Microbial Iron Uptake .3.1 Introduction .3.2 Iron uptake from Siderophores .3.2.1 Siderophores .3.2.2 Iron Transport Across the Outer Membrane in Gram–negative Bacteria .3.2.3 Transport across the periplasm and cytoplasmic membrane in Gram–negative Bacteria .3.2.4 Iron uptake by Gram–positive Bacteria .References .4. Iron Acquisition by Pathogens .4.1 Introduction .4.2 Host Defense Mechanisms, Nutritional Immunity .4.3 Pathogenicity and PAIs .4.4 Pathogen Specific Iron Uptake Systems .4.4.1 Siderophores Associated with Virulence .4.4.2 Transferrin/Lactoferrin Iron Uptake .4.4.3 Haem Iron Uptake .4.4.4 Ferrous Iron Uptake .4.4.5 Ferric Citrate Uptake by Bacillus Cereus .4.5 Role of Fur, etc in virulence .4.6 Role of Pathogen ECF Sigma Factors .4.7 Fungal Pathogens .References .5. Iron Uptake by Plants and Fungi .5.1 Iron Uptake by Plants .5.1.1 Introduction .5.1.2 Genome sequencing .5.1.3 Iron Acquisition by the Roots of Plants .5.1.3.1 Non–gramminaceous plants .5.1.3.2 Gramminaceous plants .5.1.4 Long distance iron transport .5.2 Iron metabolism and homeostasis in Plants .5.2.1 New Tools in Plant Research .5.2.2 Intracellular iron metabolism .5.2.3 Plant iron homeostasis .5.2.4 Diurnal regulation of iron homeostasis .5.3 Iron Uptake Metabolism and Homeostasis in Fungi .5.3.1 Introduction .5.3.2 High and low affinity iron uptake pathways .5.3.3 Iron uptake from siderophores .5.3.3 Iron metabolism and homeostasis .References .6. Cellular Iron Uptake and Export in Mammals .6.1 The Transferrins .6.1.1 Introduction .6.1.2 The transferrin family .6.1.3 Structure of transferrins .6.1.4 Transferrin iron binding .6.1.5 Binding of other metals by transferrin .6.1.6 Transferrin–bound iron uptake .6.2 Cellular Iron Uptake .6.2.1 The transferrin receptors .6.2.2 The transferrin to cell cycle and iron release .6.2.3 Iron uptake from other sources .6.3 Cellular Iron Export .References .7. Mammalian iron metabolism and dietary iron absorption .7.1 An overview of mammalian iron metabolism .7.1.1 Introduction .7.1.2 The way different cells handle iron .7.2 Mammalian iron absorption .7.2.1 Introduction .7.2.2 The intestinal mucosa .7.2.3 Sources of dietary iron .7.2.4 Iron loss and effects on uptake .7.3 Molecular mechanisms of mucosal iron absorption .7.3.1 Iron uptake at the apical pole .7.3.2 Iron transit through and storage in enterocytes .7.3.3 Iron efflux across the basolateral membrane .7.4.4 Regulation of iron absorption. .References .8. Intracellular iron utilisation .8.1 Introduction .8.1.1 Introduction intracellular iron pools .8.1.2 The cytosolic labile iron pool (LIP) .8.1.3 Distribution of iron in the cytosol .8.1.4 Other intracellular iron pools .8.2 Miochondrial iron metabolism .8.2.1 Mitochondrial iron uptake and storage .8.2.2 Mitochondrial Fe–S protein biogenesis .8.2.3 Maturation of cytosolic and nuclear Fe–S proteins .8.2.4 Haem biosynthesis .8.3 Haem oxygenase .8.3.1 Structure and catalytic cycle .8.3.2 Activation of haem oxygenase 1 .References .9. Iron storage proteins .9.1 Introduction .9.2 The ferritin superfamilyand haemosiderins .9.2.1 The ferritin superfamily .9.2.2 Structure of mammalian ferritins .9.2.3 Plant and bacterial ferritins .8.2.4 Dps proteins and rubrerythrins .9.2.5 The mineral core .9.2.5 Haemosiderins .9.3 Iron uptake and release from ferritins and Dps proteins .9.3.1 Iron uptake in ferritins .(i) entry of Fe (II) into the protein shell .(ii) oxidation of Fe2+ by ferroxidase sites .(iii) mineralisation of the iron core .9.3.2 Iron uptake in Dps proteins .9.3.3 Iron release from ferritin and Dps proteins .References .10. Cellular and systemic iron homeostasis .10.1 Cellular iron homeostasis .10.1.1 Translational regulation of protein synthesis .10.1.2 The IRE/IRP system .10.1.3 The IREs distribution and structure .10.1.4 Structural features of IRP1 and 2 .10.1.5 The IRE/IRP system revisited iron controls iron .10.1.6 Metabolic consequences of mutations in IREs .10.2 Systemic iron homeostasis .10.2.1 Introduction .10.2.2 Hepcidin, the key player .10.2.3 Factors which regulate hepcidin synthesis .10.2.3.1 Iron availability .10.2.3.2 Inflammatory stimuli .10.2.3.3 Erythropoietic demand .10.2.3.4 Hypoxia .10.2.3.5 Endocrine signals .10.3 Integration of iron homeostasitic systems .References .11. Iron deficiency, iron overload and therapy .Introduction .11.1 Iron deficiency anaemia (IDA) .11.1.1 Introduction the size of the problem .11.1.2 Causes of IDA .11.1.3 Clinical stages and diagnosis .11.1.4 Therapeutic approaches .11.1.5 Anaemia of chronic disease (ACD), iron refractory (IRIDA) and the anaemia of chronic kidney disease (CKD) .11.2 Hereditary iron overload .11.2.1 Introduction .11.2.2 Hereditary haemochromatosis .11.2.3 Causes of hereditary haemochromatosis .11.2.4 Types of haemochromatosis .11.2.4.1 HFE–related (Type 1) haemochromatosis .11.2.4.2 Juvenile (Type 2) haemochromatosis .11.2.4.3 TfR2–related (Type 3) haemochromatosis .11.2.4.4 Ferroportin disease– Type 4 haemochromatosis .11.2.5 Therapy of hereditary haemochromatosis .11.3 Acquired Iron overload .11.3.1 Introduction causes of acquired iron overload .11.3.2 Mechanisms of iron toxicity .11.3.3 Evaluation of iron overload .11.3.4 Chelation therapy for aquired iron overload .11.3.5 Other therapeutic approaches .12. Iron and Immunity .12.1 Introduction .12.2.1 Innate immunity .12.2 The key role of macrophages .12.2.1 Overview .12.2.2 Macrophage phenotypes .12.2.3 Microglia .12.3 Effect of iron status on phagocytic cell function .12.3.1 Iron deficiency .12.3.2 Iron overload .12.4 Effect of phagocytic cell function on iron metabolism .12.5 Effector molecules of the innate immune system .12.5.1 Toll–like receptors .12.5.2 NFkappa B .12.5.3 Hypoxia Inducible Factor .12.5.4 Haem Oxygenase .12.5.5 DMT1/Nramp1 .12.6 Adaptive Immunity .12.7 Immune Function and other factors .12.8 Concluding remarks .References .13. Iron and oxidative stress .13.1 Oxidative stress .13.1.1 Introduction milestones in the history of life .13.1.2 Reactive oxygen and nitrogen species (ROS and RNS) .13.1.3 Cellular defense mechanisms against oxidative stress .13.1.4 Role of ROS and RNS in cell signalling .13.1.5 ROS, RNS and oxidative damage .14. Interactions between Iron and Other Metals .14.1 Introduction .14.2 Iron Interactions with Essential Metals .14.2.1 Copper .14.2.2 Zinc .14.2.3 Cobalt .14.2.4 Manganese .14.2.5 Calcium .14.3 Iron Interactions with Toxic Metals .14.3.1 Lead .14.3.2 Cadmium .14.3.3 Aluminium .References .15. Iron Homeostasis and Neurodegeneration .15.1 Introduction .15.2 Brain iron .15.2.1 Brain iron homeostasis .15.2.2 Aging and brain iron content .15.3 Iron and neurodegeneration .15.3.1 Introduction .15.3.2 Adverse effects of iron in neurodegeneration .15.4 Neurodegeneration with Brain Iron Accumulation .15.4.1. Aceruloplasminaemia .15.4.2 Neuroferritinopathy .15.4.3 Other NBIAs .15.5 Other monogenic neurodegenerative diseases with iron accumulation .15.5.1 Huntington s Disease .15.5.2 Friedreich s Ataxia .15.6 Neurodegeneration involving multiple genes with iron accumulation .15.6.1 Parkinson s disease .15.6.2 Alzheimer s disease .15.6.3 Multiple Sclerosis .15.7 Intracerebral haemorrhage .References .Index

• ISBN: 978-1-118-92561-4
• Editorial: Wiley–Blackwell
• Encuadernacion: Cartoné
• Páginas: 496
• Fecha Publicación: 03/06/2016
• Nº Volúmenes: 1
• Idioma: Inglés