Yehuda / Mostofsky Iron Deficiency and Overload

From Basic Biology to Clinical Medicine
1. Auflage 2010
ISBN: 978-1-59745-462-9
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 376 Seiten

Reihe: Nutrition and Health

Iron deficiency is ever-present among all populations throughout the world irrespective of race, culture, or ethnic background. Even with the latest advances in medicine, improved nutrition, and the ready availability of cheap oral iron, there is still no satisfactory explanation for the widespread occurrence of iron deficiency or for the absence of an effective treatment. Iron Deficiency and Overload: From Biology to Clinical Medicine is an important new text that provides a timely review of the latest science concerning iron metabolism as well as practical, data-driven options to manage at-risk populations with the best accepted therapeutic nutritional interventions. Chapter topics reflect the excitement in current theoretical development and laboratory activity in this area. The distinguished authors address their presentations to professionals and graduate students who need to be better informed about the concepts, methodologies, and current status of the field. Iron Deficiency and Overload: From Biology to Clinical Medicine is an essential text that presents a sampling of the major issues in iron research, from the most basic research level to human applications.

Autoren/Hrsg.

Yehuda, Shlomo

Mostofsky, David I.

Inhaltsverzeichnis

1;Series Editor Introduction;6
2;Preface;11
3;Contents;13
4;Contributors;15
5;Part 1: Iron Biochemistry and Metabolism;17
5.1;The Cellular Physiology of Iron;18
5.1.1;1. Introduction;18
5.1.2;2. What is Iron Used for in the Cell?;22
5.1.3;3. Cellular Iron Uptake;24
5.1.3.1;3.1. Transferrin-Bound Iron Delivery to Cells;25
5.1.3.2;3.2. Iron Movement Across the Endosomal and Plasma Membranes - Divalent Metal-Ion Transporter 1;27
5.1.3.3;3.3. Non-transferrin-Bound Iron Uptake;27
5.1.3.4;3.4. The Uptake of Other Forms of Iron;28
5.1.4;4. Intracellular Iron Utilization;29
5.1.5;5. Intracellular Iron Storage;31
5.1.6;6. Cellular Iron Release;32
5.1.7;7. Regulation of Cellular Iron Metabolism;33
5.1.8;8. Systemic Iron Metabolism;35
5.1.8.1;8.1. Systemic Iron Transport;35
5.1.8.2;8.2. Regulation of Systemic Iron Homeostasis;35
5.1.9;9. Conclusion;36
5.1.10;References;37
5.2;Regulation of Iron Absorption and Distribution;45
5.2.1;1. Introduction and Scope of Review;45
5.2.2;2. Iron Uptake and Release by Cells;46
5.2.3;3. Mechanisms of Iron Absorption and Loss by Mammals;47
5.2.4;4. Iron Transport Round the Body and Tissue Uptake;49
5.2.5;5. Regulation at the Cellular Level;52
5.2.6;6. Regulation of Whole Body Iron Status;53
5.2.7;7. Hepcidin in the Regulation of Iron Absorption and Distribution;55
5.2.8;8. Concluding Overview and Unknowns;56
5.2.9;References;57
5.3;The Role of Hepcidin in Iron Homeostasis;64
5.3.1;1. Introduction;64
5.3.2;2. The Interaction of The Hormone Hepcidin and Its Receptor Ferroportin Regulates Systemic Iron Metabolism;65
5.3.2.1;2.1. Hepcidin;65
5.3.2.2;2.2. Ferroportin;65
5.3.2.3;2.3. Regulation of Ferroportin by Hepcidin;65
5.3.2.4;2.4. Structure-Function Analysis of Hepcidin;66
5.3.2.5;2.5. Hepcidin Catabolism;66
5.3.2.6;2.6. Cellular Regulation of Ferroportin;66
5.3.3;3. Regulation of Hepcidin Synthesis by Iron;67
5.3.3.1;3.1. Hereditary Hemochromatosis Proteins Are Hepcidin Regulators;67
5.3.3.2;3.2. Hemojuvelin;67
5.3.3.3;3.3. The Bone Morphogenetic Protein (BMP) Pathway in Hepcidin Regulation;68
5.3.3.4;3.4. Transferrin and Transferrin Receptors 1 and 2;68
5.3.3.4.1;3.4.1. TfR1;68
5.3.3.4.2;3.4.2. TfR2;69
5.3.3.4.3;3.4.3. Holotransferrin;69
5.3.3.4.4;3.4.4. Iron Sensing;69
5.3.3.5;3.5. HFE;69
5.3.3.6;3.6. A Model of Hepcidin Regulation;70
5.3.4;4. Regulation of Systemic Iron Metabolism and Hepcidin Synthesis by Hypoxia-Inducible Transcription Factors;70
5.3.4.1;4.1. Gene Regulation by Hypoxia;70
5.3.4.2;4.2. Iron and Hepcidin Regulation by Hypoxia;70
5.3.4.3;4.3. HIF Involvement in Hepcidin Suppression During Iron Deficiency;71
5.3.5;5. Regulation of Plasma Iron and Of Hepcidin Synthesis by Inflammation;71
5.3.5.1;5.1. Hepcidin and the Acute Hypoferremia of Inflammation;71
5.3.5.2;5.2. Hepcidin and Anemia of Inflammation;71
5.3.5.3;5.3. Regulation of Hepcidin During Infection and Inflammation;72
5.3.5.4;5.4. Regulation of Hemojuvelin by Inflammation;72
5.3.6;6. Regulation of Hepcidin Synthesis by Erythropoietic Activity;72
5.3.6.1;6.1. Erythropoiesis Suppresses Hepcidin Synthesis;72
5.3.6.2;6.2. Hepcidin Suppression in Expanded but Ineffective Erythropoiesis;72
5.3.7;7. Summary;73
5.3.8;References;73
5.4;Iron as Nutrient: Strategies for Iron Acquisition and Usage by Pathogenic Microorganisms;78
5.4.1;1. Iron as Nutrient;78
5.4.1.1;1.1. The Importance of Fe Metabolism;78
5.4.1.2;1.2. Fe and Pathogenic Bacteria;79
5.4.2;2. Post-Synthetic Modification of Siderophores In Pathogenic Bacteria;79
5.4.2.1;2.1. Enterobactin Biosynthesis and Secretion;79
5.4.2.2;2.2. Glucosylated Enterobactin Is a Virulence Factor in Pathogenic Bacteria;80
5.4.3;3. Intracellular Iron Homeostasis In Bacteria;82
5.4.3.1;3.1. Small Regulatory RNAs and Environmental Stresses;82
5.4.3.2;3.2. Role and Mechanism of the sRNA RyhB During Fe Starvation;83
5.4.3.3;3.3. Roles of RyhB in Biofilms, Chemotaxis, and Acid Resistance;84
5.4.3.4;3.4. Similar Regulatory Mechanism in Other Species;85
5.4.3.5;3.5. Siderophore Biosynthesis and RyhB;85
5.4.3.6;3.6. Concluding Remarks;86
5.4.4;References;86
5.5;Iron as a Drug and Drug-Drug Interactions;90
5.5.1;1. Pharmacology;90
5.5.2;2. Oral Iron Preparations;91
5.5.2.1;2.1. Bioavailability;91
5.5.2.2;2.2. Adverse Drug Events with Oral Iron Preparations;91
5.5.2.3;2.3. Drug Interactions;92
5.5.3;3. Parenteral Iron Preparations;92
5.5.3.1;3.1. Iron Dextran;92
5.5.3.2;3.2. Iron Sucrose (Iron Saccharate);94
5.5.3.3;3.3. Ferric Gluconate;94
5.5.3.4;3.4. Adverse Drug Events with Parenteral Iron Preparations;94
5.5.4;4. Toxicity;95
5.5.4.1;4.1. Acute Toxicity;95
5.5.4.2;4.2. Clinical Effects;95
5.5.4.3;4.3. Range of Toxicity;96
5.5.4.4;4.4. Treatment;96
5.5.4.5;4.5. Chronic Toxicity;97
5.5.4.6;4.6. Clinical Effects;97
5.5.4.7;4.7. Range of Toxicity;98
5.5.4.8;4.8. Treatment;99
5.5.5;5. Conclusion;100
5.5.6;References;100
6;Part 2: Iron Overload and Deficiency Pathologies;105
6.1;Iron Deficiency and Excess in the Brain: Implications for Cognitive Impairment and Neurodegeneration;106
6.1.1;1. Nutritional Iron Deficiency and its Neurochemical Aspect;107
6.1.2;2. The Impact of Nutritional Iron Deficiency on Brain Iron;108
6.1.3;3. Early Iron Deficiency and its Consequence on Brain Function and Behavior;111
6.1.4;4. Brain Iron Deficiency and Dopamine-Endogenous Opiate Interaction and Function;112
6.1.5;5. Iron and Zinc Interaction in the Hippocampus;113
6.1.5.1;5.1. The Normal Development of Ferritin Distribution in the Hippocampus;113
6.1.5.2;5.2. Effects of Iron Deficiency on Distribution of Ferritin in the Hippocampus;113
6.1.5.3;5.3. Effects of Zinc Alone and Zinc Added to Iron Therapy;114
6.1.6;6. Brain Iron and Parkinson’S Disease;116
6.1.6.1;6.1. Transition Metals in Parkinson’s Disease;116
6.1.7;7. Iron in Parkinsonian Brain;117
6.1.8;8. Sources of Iron and its Interaction with Neuromelanin;119
6.1.9;9. Consequences of Iron Overload in the Parkinsonian Substantia Nigra;122
6.1.10;10. Conclusion;124
6.1.11;References;125
6.2;Brain Iron Deposition in Aging and Disease: Role of HO-1;135
6.2.1;7.1. Introduction;135
6.2.2;7.2. Iron Deposition in the Aging And Degenerating CNS;136
6.2.2.1;7.2.1. Aging;136
6.2.2.2;7.2.2. Alzheimer’s Disease;137
6.2.2.3;7.2.3. Parkinson’s Disease;137
6.2.2.4;7.2.4. Other Neurological Disorders;137
6.2.2.5;7.2.5. Glial Senescence and Iron Sequestration;138
6.2.2.5.1;7.2.5.1. The Cysteamine Model;138
6.2.2.5.2;7.2.5.2. Mitochondrial Precursors of Senescent Glial Granules;138
6.2.2.5.3;7.2.5.3. Non-Transferrin Iron Sequestration in ‘‘Stressed’’ Astroglial Mitochondria;139
6.2.3;7.3. Heme Oxygenase-1 and Brain Iron Homeostasis;139
6.2.3.1;7.3.1. Heme Oxygenase;139
6.2.3.2;7.3.2. HO-1 and Astroglial Iron;140
6.2.3.3;7.3.3. HO-1 and Human Brain Aging;142
6.2.3.4;7.3.4. HO-1 and Alzheimer’s Disease;142
6.2.3.5;7.3.5. HO-1 and Parkinson’s Disease;143
6.2.3.6;7.3.6. HO-1 and Other Human CNS Disorders;145
6.2.4;7.4. Conclusions;145
6.2.5;References;146
6.3;Iron Deficiency and Neuropharmacology;150
6.3.1;1. Introduction;150
6.3.2;2. Monoamines;151
6.3.2.1;2.1. Dopamine;151
6.3.2.1.1;2.1.1. Dopaminergic Brain Regions and Consequences of ID;151
6.3.2.1.2;2.1.2. Synthesis;151
6.3.2.1.3;2.1.3. Catabolism;153
6.3.2.1.4;2.1.4. Dopamine Receptors;153
6.3.2.1.5;2.1.5. DA Transport;154
6.3.2.1.6;2.1.6. D2R-DAT Link;155
6.3.2.1.7;2.1.7. Iron Deficiency During Development;155
6.3.2.2;2.2. Norepinephrine;156
6.3.2.2.1;2.2.1. Synthesis;156
6.3.2.2.2;2.2.2. Degradation and Transport;157
6.3.2.3;2.3. Serotonin;158
6.3.2.3.1;2.3.1. Synthesis;158
6.3.2.3.2;2.3.2. Transport;158
6.3.2.3.3;2.3.3. Receptors;159
6.3.2.3.4;2.3.4. Catabolism;159
6.3.2.4;2.4. GABA/Glutamate;159
6.3.2.4.1;2.4.1. Synthesis;160
6.3.2.4.2;2.4.2. Receptors;161
6.3.2.4.3;2.4.3. Iron Deficiency and Drugs of Abuse;161
6.3.2.4.4;2.4.4. Adhd;161
6.3.2.5;2.5. Endorphins;162
6.3.2.6;2.6. Estrogen;162
6.3.3;3. Conclusions;162
6.3.4;References;163
6.4;Peripheral Effects of Iron Deficiency;168
6.4.1;1. Historical Account of Iron Deficiency and its Clinical Manifestations;168
6.4.2;2. Prevalence of Iron Deficiency and its Causes;170
6.4.3;3. Pathogenesis of the Manifestations of Iron Deficiency;172
6.4.3.1;3.1. Proteins and Enzymes;172
6.4.3.2;3.2. Epithelial Cells and Skeleton;173
6.4.4;4. Laboratory Evaluation of Iron Deficiency;173
6.4.5;5. Clinical Manifestations of Iron Deficiency and Iron Deficiency Anemia;175
6.4.5.1;5.1. Clinical Manifestations of Anemia;175
6.4.5.2;5.2. Effects on the Hematopoietic System;175
6.4.5.3;5.3. Effects on Non-hematopoietic Systems;177
6.4.5.4;5.4. Tongue and Mouth;177
6.4.5.5;5.5. Hypopharynx and Esophagus;178
6.4.5.6;5.6. Stomach;179
6.4.5.7;5.7. Nails;180
6.4.5.8;5.8. Hair;181
6.4.5.9;5.9. Other Manifestations;181
6.4.6;References;182
6.5;Iron-Metabolism in Neurons of the Motor System of the Central Nervous System: Lessons from Iron Deficiency and Overloading Pathologies;190
6.5.1;1. Introduction;190
6.5.2;2. Neuronal Iron Metabolism in the Normal Brain;191
6.5.3;3. Iron Homeostasis in Myelin-Forming Cells;195
6.5.4;4. Cerebral Iron Homeostasis in Iron Deficiency;196
6.5.5;5. Management of Iron in the Brain in Conditions with Raised Cerebral Iron;197
6.5.6;6. Conclusions and Outlook;199
6.5.7;References;199
6.6;The Effects of Brain Iron Deficiency on Cognitive and Behavioral Aspects;203
6.6.1;1. Introduction;203
6.6.2;2. Iron in the Brain;204
6.6.3;3. The Role of Iron in Myelination;205
6.6.4;4. Brain Iron and Brain Dopamine;205
6.6.5;5. Iron and Schizophrenia;206
6.6.6;6. Iron Deficiency, Learning, and Hippocampus Integrity;206
6.6.6.1;6.1. Animal Studies;206
6.6.6.2;6.2. Human Studies;208
6.6.7;7. Iron Deficiency and Pretems;208
6.6.8;8. Long-Term Effects of Transient Iron Deficiency Period;209
6.6.9;9. The Auditory System and Iron Deficiency;210
6.6.10;10. Iron Deficiency and the Endocrine System;210
6.6.11;11. Iron Deficiency and the Immune System;211
6.6.12;12. Conclusion;211
6.6.13;References;212
6.7;Stress, Immunology, and Cytokines;215
6.7.1;1. Characteristics of Stress;215
6.7.2;2. Stress, the CNS, and the Immune System;216
6.7.3;3. Cytokines as Mediators of Neuroimmune Communication;216
6.7.4;4. The Interaction Between Cytokines and the HPA Axis;218
6.7.5;5. Cytokines in the CNS;219
6.7.6;6. Inflammatory Cytokines, Glucocorticoids, and Human Disease;220
6.7.7;7. Stress and TH1/TH2 Subsets;220
6.7.8;8. Stress, Glucocorticoids, and TH1/TH2 Balance;222
6.7.9;9. Stress, Inflammation, and Autoimmune Diseases;222
6.7.10;10. T-helper Cell Commitment Toward Specific Lineages: the Role of the TH17 Subset in Inflammation;223
6.7.11;11. Summary;224
6.7.12;References;224
7;Part 3: Diagnostic and Clinical Aspects in CNS Disorders;229
7.1;MRI of Brain Iron and Neurodegenerative Diseases: A Potential Biomarker;230
7.1.1;1. Introduction;230
7.1.2;2. Other Forms of Iron in the Brain;234
7.1.3;3. Biology of Brain Iron and Copper;234
7.1.4;4. Inborn Errors of Brain Iron Metabolism;238
7.1.5;5. Mri Techniques for Imaging Brain Iron;239
7.1.6;6. Brain Iron Imaging at Seven Tesla;241
7.1.7;7. Conclusion;242
7.1.8;References;243
7.2;Alzheimer’s Dementia;248
7.2.1;1. Clinical and Pathological Features of Alzheimer’s Disease;248
7.2.2;2. Iron and the Pathogenesis of Alzheimer’s Disease;249
7.2.3;3. Evidence for Dysregulation of Brain Iron Homeostasis in Ad Patients;250
7.2.4;4. Experimental Evidence for a Pathogenic Role for Iron in AD;250
7.2.5;5. Therapeutic Implications of Iron in Ad Pathogenesis;252
7.2.6;References;253
7.3;Inherited Disorders of Brain Iron Homeostasis;257
7.3.1;15.1. Human Iron Physiology: an Overview;257
7.3.2;15.2. Genetic Disorders of CNS Iron Homeostasis;260
7.3.2.1;15.2.1. Friedreich’s Ataxia;260
7.3.2.2;15.2.2. Pantothenate Kinase-2-Associated Neurodegeneration;263
7.3.2.3;15.2.3. Aceruloplasminemia;265
7.3.2.4;15.2.4. Neuroferritinopathy;268
7.3.2.5;15.2.5. X-Linked Sideroblastic Anemia with Ataxia;270
7.3.2.6;15.2.6. IRP2 Deficiency;271
7.3.2.7;15.2.7. Differential Diagnosis;272
7.3.3;15.3. Hemochromatosis and the CNS;272
7.3.3.1;15.3.1. General Considerations;272
7.3.3.2;15.3.2. Mutant HFE and Alzheimer’s Disease;273
7.3.3.3;15.3.3. Mutant HFE and Parkinson’s Disease;274
7.3.3.4;15.3.4. Mutant HFE and Amyotrophic Lateral Sclerosis;275
7.3.3.5;15.3.5. Mutant HFE and Ischemic Stroke;275
7.3.4;15.4. Concluding Remarks;275
7.3.5;References;276
8;Part 4: Public Health Issues;283
8.1;Iron and Heart Disease: A Review of the Epidemiologic Data;284
8.1.1;1. Introduction;284
8.1.2;2. Serum Measures of Body Iron Stores;285
8.1.3;3. Body Iron Stores And Risk of Heart Disease: The Epidemiologic Data;287
8.1.3.1;3.1. Cohort Studies Based on Serum Ferritin;287
8.1.3.2;3.2. Cohort Studies Based on TS;291
8.1.3.3;3.3. Case-Control or Cross-Sectional Studies;293
8.1.3.4;3.4. Dietary Iron and CHD Risk;294
8.1.3.5;3.5. Blood Donor Studies and Iron and Oxidized LDL Cholesterol;294
8.1.4;4. Clinical Trials: Reducation of Iron Stores and Cvd Risk;296
8.1.5;5. Iron Overload and Chd Risk;297
8.1.6;6. Summary;297
8.1.7;7. Recommendations;298
8.1.8;References;298
8.2;Global Concept of Iron Deficiency;304
8.2.1;1. Pregnancy and The Newborn;306
8.2.2;2. Malaria;307
8.2.3;3. Latent Iron Deficiency;307
8.2.4;4. Management Strategies;309
8.2.5;5. Burden of Disease in A Population;310
8.2.6;6. Effect on Blood Transfusion Services;312
8.2.7;7. Tests in Under-Resourced Countries;313
8.2.8;8. Haemoglobinometry;314
8.2.9;References*;315
8.3;Nutritional Iron Deficiency in Early Childhood;318
8.3.1;1. Introduction;318
8.3.2;2. Defining the Prevalence of Iron Deficiency;319
8.3.3;3. Risk Factors for Iron Deficiency in Early Childhood;320
8.3.4;4. Iron Deficiency and Deficits in Psychomotor Development;322
8.3.5;5. Iron Deficiency and Susceptibility to Infection;324
8.3.6;6. Prevention of Iron Deficiency in Childhood;325
8.3.6.1;6.1. Dietary Education;325
8.3.6.2;6.2. Iron Supplementation;325
8.3.6.3;6.3. Iron Fortification of Food;326
8.3.6.4;6.4. Screening for Anaemia;327
8.3.7;7. Conclusions;327
8.3.8;References;328
8.4;Iron and Women’s Health;332
8.4.1;1. Introduction;332
8.4.2;2. Basic Biochemical Functions;334
8.4.2.1;2.1. Major Heme Proteins;334
8.4.3;3. Metabolism;334
8.4.3.1;3.1. Chemical Forms and Absorption of Iron;335
8.4.3.2;3.2. Transport;336
8.4.3.3;3.3. Storage;336
8.4.3.4;3.4. Excretion;336
8.4.4;4. Clinical Values of Iron Status;337
8.4.4.1;4.1. Iron Deficiency;337
8.4.4.2;4.2. Iron Deficiency Anemia;338
8.4.4.3;4.3. Iron Supplementation and Fortification;338
8.4.4.4;4.4. Iron and Ovulation;339
8.4.4.5;4.5. Iron Overload;339
8.4.4.6;4.6. Lifestyle Factors That Can Affect Women’s Iron Status;339
8.4.5;5. Pregnancy and Lactation;340
8.4.5.1;5.1. Iron Requirements;340
8.4.5.2;5.2. Iron Deficiency Anemia;341
8.4.5.3;5.3. Iron Supplementation;341
8.4.5.4;5.4. Maternal Iron Supplementation, Pregnancy Outcomes, and Infant Iron Status;343
8.4.5.5;5.5. Maternal Post-pregnancy Iron Status;343
8.4.5.6;5.6. Lactation;345
8.4.6;6. Menopause;345
8.4.6.1;6.1. Intake;345
8.4.6.2;6.2. Iron Deficiency and Iron Overload in Older Women;346
8.4.6.3;6.3. Iron Supplement Use in Postmenopausal Women;347
8.4.7;7. Diseases Related to Iron Status;347
8.4.7.1;7.1. Metabolic Syndrome and Type 2 Diabetes;347
8.4.7.2;7.2. Osteoporosis;349
8.4.8;8. Conclusions;350
8.4.9;References;353
9;Appendix A: Reference Ranges for Common Laboratory Assays of Iron Metabolism;356
9.1;Introductory Comments;356
9.2;References;359
10;Appendix B: Nutritional Sources of Iron;360
10.1;Introductory Comments;360
10.2;References;359
11;Subject Index;363
12;About the Editors;376
13;About the Series Editor;377