Inorganic Biochemistry of Iron Metabolism: From Molecular Mechanisms to Clinical Consequences, Second Edition

355 Pages·2001·4.98 MB·English

by  Robert Crichton(auth.)

InorganicBiochemistryofIronMetabolism:FromMolecularMechanismsto
ClinicalConsequences.2e
RobertCrichton
Copyright2001JohnWiley&SonsLtd
ISBNs:0-471-49223-X(Hardback);0-470-84579-1(Electronic)
Inorganic Biochemistry
of Iron Metabolism
Inorganic Biochemistry
of Iron Metabolism
From Molecular Mechanisms
to Clinical Consequences
Second Edition
Robert Crichton
Universite´ CatholiquedeLouvain,Belgium
Withthecollaborationof
JohanR.Boelaert,VolkmarBraun,KlausHantke,JoJ.M.Marx,
ManuelaSantosandRobertaWard
JOHN WILEY & SONS, LTD
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LibraryofCongressCataloguing-in-PublicationData
Crichton,RobertR.
Inorganicbiochemistryofironmetabolism:frommolecularmechanismstoclinical
consequences/RobertCrichton;withthecollaborationofJohanBoelart...[etal.].--2nded.
p.cm.
Includesbibliographicalreferencesandindex.
ISBN0-471-49223-X(alk.paper)
1.Iron--Metabolism.2.Ironproteins.3.Iron--Metabolism--Disorders.I.Boelart,
Johan.II.Title.
QP535.F4C752001
(cid:1)
572.5174--dc21
2001026202
BritishLibraryCataloguinginPublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
ISBN0-471-49223-X
Typesetin10.5/12.5ptPalatinobyLaserWords,Chennai,India
PrintedandboundinGreatBritainbyAntonyRowe,Chippenham,Wiltshire.
Thisbookisprintedonacid-freepaperresponsiblymanufacturedfromsustainable
forestryinwhichatleasttwotreesareplantedforeachoneusedforpaperproduction.
Contents
Preface xv
1
Solution Chemistry of Iron in Biological Media
1
1.1
AqueousSolutionChemistryofIron 1
1.2
OxygenFreeRadicals 2
1.3
IronHydrolysis–AUbiquitousPhenomenon 6
1.4
HydrolysisofIron(III)inAcidMedia–Formation
ofPolynuclearSpecies 6
1.5
FormationofPrecipitates 8
1.5.1 AgeingofAmorphousFerrihydritetoMore-crystallineProducts 9
1.6
Biomineralization 11
1.6.1 MagnetiteBiomineralizationbyMagnetotacticBacteria 11
1.7
References 14
2
The Importance of Iron for Biological Systems
17
2.1
Introduction 17
2.2
PhysicalTechniquesfortheStudyofIroninBiologicalSystems 20
2.3
Haemoproteins 22
2.3.1 OxygenCarriers 22
2.3.2 ActivatorsofMolecularOxygen 25
2.3.3 ElectronTransportProteins 31
vi Contents
2.4
Iron–SulfurProteins 34
2.5
OtherIron-containingProteins 37
2.5.1 MononuclearNon-haemIronEnzymes 40
Dioxygenases 40
Hydroxylases 41
a-Ketoacid-dependentEnzymes 42
IsopenicillinNSynthase 43
SuperoxideDismutases 43
2.5.2 DinuclearNon-haemIronEnzymes 44
(m-Carboxylato)diironProteins 45
2.6
References 48
3
Microbial Iron Uptake
49
3.1
Introduction 49
3.2
Siderophores 51
3.2.1 FhuA-mediatedFerrichromeTransportAcross
theOuterMembrane–ofE.coli 54
3.2.2 FhuAasanAntibioticTransporter 58
3.2.3 TransportofFerrichromeAcrosstheCytoplasmicMembrane 58
3.2.4 VarietyofFe3+ TransportSystemsinBacteria 63
3.3
FerrousIronTransportSystems 63
3.4
IronMetabolism 64
3.5
IronRegulationinBacteria–theFurProtein 65
3.5.1 TheFurRegulon 66
3.5.2 SiderophoreBiosynthesisandUptake 66
3.5.3 IronMetabolismandOxidativeStressResponse 70
3.5.4 GenesRegulatedbyFur 71
3.5.5 Virulence-AssociatedGenes 71
3.5.6 Fur-likeProteins 71
DtxR-likeRegulators 72
3.5.7 RegulationbyFe3+ Siderophores 73
3.5.8 RegulationofOuterMembraneTransporterSynthesis
byPhaseVariation 74
3.5.9 Iron-relatedBacterialVirulence 75
3.6
Acknowledgements 76
3.7
References 76
Contents vii
4
Iron Uptake by Plants and Yeast
83
4.1
IronAcquisitionbyPlants 83
4.1.1 Introduction 83
4.1.2 IronAcquisitionbytheRootsofPlants 84
Dicotyledons 84
andNon-grassMonocotyledons(StrategyI)–FerrousIronTransport
GraminaceousPlants(Strategy–FerricIronTransport 88
MutantsAffectedinIronTransport 90
4.2
PlantFerritins 91
4.2.1 DevelopmentalRegulationofFerritinSynthesis 91
4.2.2 Iron-regulatedExpressionofFerritinGenes 92
4.3
IronAcquisitionbyYeast 92
4.3.1 Introduction–PathwaysforIronUptake 93
4.3.2 CellSurfaceReductases 93
4.3.3 IronUptakeAcrossthePlasmaMembrane 94
LowAffinityIron-TransportSystem 94
HighAffinityIron-TransportSystem 95
SMFFamilyofTransporters 97
Siderophore-mediatedIronUptake 97
RecoveryofIronfromtheVacuole 98
4.4
IntracellularIronMetabolism 99
4.4.1 MitochondrialIronTransport 100
4.4.2 IronStorageinS.cerevisiae 101
4.5
IronTransportinOtherFungi 101
4.6
References 102
5
Cellular Iron Uptake in Mammals
107
5.1
TheTransferrins 107
5.1.1 StructureofTransferrins 108
5.1.2 TransferrinIronBindingandRelease 111
5.2
IronUptakebyMammalianCells–UptakeofTransferrin-boundIron 115
5.2.1 TheTransferrinReceptor 115
5.2.2 TransferrinBindingtoItsReceptor 118
5.2.3 TransferrinReceptorBindingtoHereditary
HaemochromatosisProteinHFE 120
viii Contents
5.2.4 TheTransferrin-to-cellCycle 121
5.2.5 Receptor-independentUptakeofTransferrinIron 124
5.3
IronUptakebyMammalianCells–Uptakeof
Non-transferrinBoundIron 124
5.3.1 Non-protein-BoundIron 125
5.3.2 Ferritin-boundIron 126
5.3.3 HaemopexinasanIronTransporter 126
5.4
References 127
6
Intracellular Iron Storage and Biomineralization
133
6.1
IntracellularIronStorage 133
6.1.1 Ferritin:DistributionandPrimaryStructure 134
6.1.2 Ferritin:Three-dimensionalStructure 138
L-ChainFerritins 139
H-chainFerritins 145
Bacterioferritins 146
Ferritin-likeProteins 147
6.1.3 TheMineralCore 149
6.1.4 IronDepositioninFerritin 151
IronPathwaysintoFerritin 151
IronOxidationatDinuclearCentres 152
FerrihydriteNucleationSites 154
CrystalGrowth 155
6.1.5 IronMobilizationfromFerritin 156
6.1.6 Haemosiderin 157
6.2
Biomineralization 159
6.3
References 161
7
Intracellular Iron Metabolism and Cellular
Iron Homeostasis 167
7.1
IntracellularIronMetabolism 167
7.1.1 TheLabileIronPool 167
7.1.2 HaemBiosynthesis 168
7.1.3 Friedrich’sAtaxiaandMitochondrialIronMetabolism 171
Contents ix
7.1.4 SynthesisofNon-haemIronCentres 172
7.1.5 IntracellularHaemDegradation–HaemOxygenase 174
7.2
MetalIonHomeostasis 176
7.2.1 StructuralFeaturesofIREs 178
7.2.2 HereditaryHyperferritinaemia–CataractSyndrome 180
7.2.3 mRNATranslation–IRETranslationRegulators 181
7.2.4 mRNAStability–IRETurnoverRegulators 182
7.2.5 IronRegulatoryProteins1and2 183
7.3
References 186
8
Iron Absorption in Mammals with Particular
Reference to Man 191
8.1
IronMetabolisminMan:AnOverview 191
8.2
SourcesofDietaryIroninManandtheImportanceof
LuminalFactors 192
8.3
MolecularMechanismsofMucosalIronAbsorption 194
8.3.1 IronUptakeattheApicalPole 196
8.3.2 IronTransferAcrosstheMucosalCell 197
8.3.3 ReleaseofIronattheBasolateralMembrane
andUptakebyApotransferrin 199
8.4
AModelofIronUptakeandRegulationofIronHomeostasisbythe 202
Enterocyte
8.5
References 204
9
Pathophysiology of Iron Deficiency and Iron
207
Overload in Man
9.1
Introduction:AcquiredandGeneticDisordersofIronMetabolism 207
9.2
BodyIronRegulation 208
9.2.1 CommunicationBetweenIronDonorandIronAcceptorCells 208
9.2.2 MaintenanceofIronBalanceinCells 210
x Contents
9.3
IronAbsorptioninDisordersofIronMetabolism 211
9.3.1 GenotypeandPhenotypeofAnimalandHumanIronDisorders 216
9.3.2 MacrophagesandHepatocytesinDisordersofIronMetabolism 217
9.4
IronDeficiency 220
9.4.1 PrevalenceandGlobalDistributionofIronDeficiency 220
9.4.2 AcquiredIronDeficiency 221
9.4.3 GeneticFormsofIronDeficiency 221
9.4.4 ClinicalStagesofIronDeficiency 222
9.4.5 SymptomsandSignsofIronDeficiency 223
9.4.6 TreatmentofIronDeficiency 223
9.5
IronOverload 223
9.5.1 Theb2m−/− MouseasaModelforHumanHereditary
Haemochromatosis 223
9.5.2 AdaptiveResponseofIronAbsorptioninIron-overloadDiseases 224
9.5.3 CausesofIronOverload 225
9.5.4 HeterogeneityofPhenotypesinHereditaryHaemochromatosis 225
9.5.5 FindingsinC282YHeterozygotes 227
9.5.6 HaemochromatosisandPorphyriaCutaneaTarda 227
9.5.7 TreatmentofIronOverload 228
9.6
Conclusion 228
9.7
References 229
10
Iron and Oxidative Stress
235
10.1
Introduction 235
10.2
IronandFentonChemistry 235
10.2.1 ReactiveNitrogenSpecies 236
10.3
ImportanceofCytoprotection 236
Glutathione(GSH) 237
10.3.1 GlutathioneReductase 238
10.3.2 GlutathionePeroxidase 238
10.3.3 SuperoxideDismutase 239
10.3.4 Catalase 239
10.3.5 PentosePhosphatePathway,PPP 239
10.3.6 HaemOxygenase 240
10.4
ImportanceofCellTypeinResponsetoOxidativeStress 240
10.4.1 CancerCells 241
10.4.2 NeutrophilsandMacrophages 242
Contents xi
10.5
NaturalResistance-associatedMacrophageProtein(Nramp1) 244
10.6
AgeingofCells 244
10.7
CellSignallingandIron 244
10.7.1 OxidativeStressinBacteria 245
10.7.2 OxidativeSignallinginYeast 245
10.7.3 OxidativeStressinPlants 245
10.7.4 OxidativeStressinMammalianCells 246
10.8
Apoptosis 249
10.9
RelationshipBetweenNFKBandNO 249
10.10
HowDoesNOandH2O2 AffecttheIron 251
RegulatoryProteinsIRP-1andIRP-2
10.11
DiseasesinwhichIncreasesinIronmaybeAssociatedwith
IncreasedOxidativeStressintheCell 252
10.11.1 IronandInflammation 252
10.12
DiseasesinwhichIronPlaysanImportantRole 252
10.12.1 GeneticHaemochromatosis 252
10.12.2 SecondaryIronOverload 253
Thalassaemia 253
HIV 253
10.13
NeurodegenerativeDiseases 253
Parkinson’sDisease 253
Alzheimer’sDisease 254
Friedrich’sAtaxia 255
10.14
References 255
11
Iron and Infection
259
11.1
Introduction 259
11.2
MicrobialStrategiestoOvercometheIron-withholdingImposedby
theHost,anditsPotentialClinicalConsequences 259
11.2.1 SiderophoreProduction 259
11.2.2 BindingofDiferric-transferrinor-lactoferrin 262
11.2.3 BindingofHaem-containingCompounds 264