Nutritional Biochemistry of the Vitamins

514 Pages·2006·5.06 MB·English

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Nutritional Biochemistry of the Vitamins
SECOND EDITION
Thevitaminsareachemicallydisparategroupofcompoundswhoseonlycommon
featureisthattheyaredietaryessentialsthatarerequiredinsmallamountsforthe
normalfunctioningofthebodyandmaintenanceofmetabolicintegrity.Metabol-
ically,theyhavediversefunctions,suchascoenzymes,hormones,antioxidants,
mediatorsofcellsignaling,andregulatorsofcellandtissuegrowthanddifferen-
tiation.Thisbookexplorestheknownbiochemicalfunctionsofthevitamins,the
extent to which we can explain the effects of deficiency or excess, and the sci-
entificbasisforreferenceintakesforthepreventionofdeficiencyandpromotion
ofoptimumhealthandwell-being.Italsohighlightsareasinwhichourknowledge
islackingandfurtherresearchisrequired.Thisbookprovidesacompactandau-
thoritativereferencevolumeofvaluetostudentsandspecialistsalikeinthefieldof
nutritionalbiochemistry,andindeedallwhoareconcernedwithvitaminnutrition,
deficiency,andmetabolism.
DavidBenderisaSeniorLecturerinBiochemistryatUniversityCollegeLondon.He
haswrittenseventeenbooks,aswellasnumerouschaptersandreviews,onvarious
aspectsofnutritionandnutritionalbiochemistry.Hisresearchhasfocusedonthe
interactionsbetweenvitaminB andestrogens,whichhasledtotheelucidationof
6
theroleofvitaminB interminatingtheactionsofsteroidhormones.Heiscurrently
6
theEditor-in-ChiefofNutritionResearchReviews.

Nutritional Biochemistry
of the Vitamins
SECOND EDITION
DAVID A. BENDER
UniversityCollegeLondon
  
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo
Cambridge University Press
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© David A. Bender 2003
This book is in copyright. Subject to statutory exception and to the provision of
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without the written permission of Cambridge University Press.
First published in print format 2003
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- 
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- 
isbn-13 978-0-521-80388-5 hardback
- 
isbn-10 0-521-80388-8 hardback
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Contents
ListofFigures pagexvii
ListofTables xxi
Preface xxiii
1 TheVitamins 1
1.1 DefinitionandNomenclatureoftheVitamins 2
1.1.1 MethodsofAnalysisandUnitsofActivity 6
1.1.2 BiologicalAvailability 8
1.2 VitaminRequirementsandReferenceIntakes 10
1.2.1 CriteriaofVitaminAdequacyandtheStagesof
DevelopmentofDeficiency 10
1.2.2 AssessmentofVitaminNutritionalStatus 12
1.2.3 DeterminationofRequirements 17
1.2.3.1 PopulationStudiesofIntake 17
1.2.3.2 Depletion/RepletionStudies 18
1.2.3.3 ReplacementofMetabolicLosses 18
1.2.3.4 StudiesinPatientsMaintainedonTotal
ParenteralNutrition 19
1.2.4 ReferenceIntakesofVitamins 19
1.2.4.1 AdequateIntake 23
1.2.4.2 ReferenceIntakesforInfantsandChildren 23
1.2.4.3 TolerableUpperLevelsofIntake 24
1.2.4.4 ReferenceIntakeFiguresforFoodLabeling 27
2 VitaminA:RetinoidsandCarotenoids 30
2.1 VitaminAVitamersandUnitsofActivity 31
2.1.1 Retinoids 31
2.1.2 Carotenoids 33
2.1.3 InternationalUnitsandRetinolEquivalents 35
v
vi Contents
2.2 AbsorptionandMetabolismofVitaminAandCarotenoids 35
2.2.1 AbsorptionandMetabolismofRetinolandRetinoicAcid 35
2.2.1.1 LiverStorageandReleaseofRetinol 36
2.2.1.2 MetabolismofRetinoicAcid 38
2.2.1.3 RetinoylGlucuronideandOtherMetabolites 39
2.2.2 AbsorptionandMetabolismofCarotenoids 40
2.2.2.1 CaroteneDioxygenase 41
2.2.2.2 LimitedActivityofCaroteneDioxygenase 42
2.2.2.3 TheReactionSpecificityofCaroteneDioxygenase 43
2.2.3 PlasmaRetinolBindingProtein(RBP) 45
2.2.4 CellularRetinoidBindingProteinsCRBPsand
CRABPs 47
2.3 MetabolicFunctionsofVitaminA 49
2.3.1 RetinolandRetinaldehydeintheVisualCycle 49
2.3.2 GenomicActionsofRetinoicAcid 54
2.3.2.1 RetinoidReceptorsandResponseElements 55
2.3.3 NongenomicActionsofRetinoids 58
2.3.3.1 RetinoylationofProteins 58
2.3.3.2 RetinoidsinTransmembraneSignaling 60
2.4 VitaminADeficiency(Xerophthalmia) 61
2.4.1 AssessmentofVitaminANutritionalStatus 64
2.4.1.1 PlasmaConcentrationsofRetinolandβ-Carotene 64
2.4.1.2 PlasmaRetinolBindingProtein 65
2.4.1.3 TheRelativeDoseResponse(RDR)Test 66
2.4.1.4 ConjunctivalImpressionCytology 66
2.5 VitaminARequirementsandReferenceIntakes 66
2.5.1 ToxicityofVitaminA 68
2.5.1.1 TeratogenicityofRetinoids 70
2.5.2 PharmacologicalUsesofVitaminA,Retinoids,
andCarotenoids 71
2.5.2.1 RetinoidsinCancerPreventionandTreatment 71
2.5.2.2 RetinoidsinDermatology 72
2.5.2.3 Carotene 72
3 VitaminD 77
3.1 VitaminDVitamers,Nomenclature,andUnitsofActivity 78
3.2 MetabolismofVitaminD 79
3.2.1 PhotosynthesisofCholecalciferolintheSkin 80
3.2.2 DietaryVitaminD 82
3.2.3 25-HydroxylationofCholecalciferol 83
3.2.4 Calcidiol1α-Hydroxylase 85
3.2.5 Calcidiol24-Hydroxylase 85
3.2.6 InactivationandExcretionofCalcitriol 86
3.2.7 PlasmaVitaminDBindingProtein(Gc-Globulin) 87
Contents vii
3.2.8 RegulationofVitaminDMetabolism 87
3.2.8.1 Calcitriol 88
3.2.8.2 ParathyroidHormone 88
3.2.8.3 Calcitonin 88
3.2.8.4 PlasmaConcentrationsofCalciumandPhosphate 89
3.3 MetabolicFunctionsofVitaminD 89
3.3.1 NuclearVitaminDReceptors 91
3.3.2 NongenomicResponsestoVitaminD 92
3.3.3 StimulationofIntestinalCalciumandPhosphateAbsorption 93
3.3.3.1 InductionofCalbindin-D 93
3.3.4 StimulationofRenalCalciumReabsorption 94
3.3.5 TheRoleofCalcitriolinBoneMetabolism 94
3.3.6 CellDifferentiation,Proliferation,andApoptosis 96
3.3.7 OtherFunctionsofCalcitriol 97
3.3.7.1 EndocrineGlands 98
3.3.7.2 TheImmuneSystem 98
3.4 VitaminDDeficiency–RicketsandOsteomalacia 98
3.4.1 NonnutritionalRicketsandOsteomalacia 99
3.4.2 VitaminD-ResistantRickets 100
3.4.3 Osteoporosis 101
3.4.3.1 Glucocorticoid-InducedOsteoporosis 102
3.5 AssessmentofVitaminDStatus 103
3.6 RequirementsandReferenceIntakes 104
3.6.1 ToxicityofVitaminD 105
3.6.2 PharmacologicalUsesofVitaminD 106
4 VitaminE:TocopherolsandTocotrienols 109
4.1 VitaminEVitamersandUnitsofActivity 109
4.2 MetabolismofVitaminE 113
4.3 MetabolicFunctionsofVitaminE 115
4.3.1 AntioxidantFunctionsofVitaminE 116
4.3.1.1 ProoxidantActionsofVitaminE 118
4.3.1.2 ReactionofTocopherolwithPeroxynitrite 119
4.3.2 NutritionalInteractionsBetweenSeleniumandVitaminE 120
4.3.3 FunctionsofVitaminEinCellSignaling 121
4.4 VitaminEDeficiency 122
4.4.1 VitaminEDeficiencyinExperimentalAnimals 122
4.4.2 HumanVitaminEDeficiency 125
4.5 AssessmentofVitaminENutritionalStatus 125
4.6 RequirementsandReferenceIntakes 127
4.6.1 UpperLevelsofIntake 128
4.6.2 PharmacologicalUsesofVitaminE 128
4.6.2.1 VitaminEandCancer 129
4.6.2.2 VitaminEandCardiovascularDisease 129
viii Contents
4.6.2.3 VitaminEandCataracts 129
4.6.2.4 VitaminEandNeurodegenerativeDiseases 129
5 VitaminK 131
5.1 VitaminKVitamers 132
5.2 MetabolismofVitaminK 133
5.2.1 BacterialBiosynthesisofMenaquinones 135
5.3 TheMetabolicFunctionsofVitaminK 135
5.3.1 TheVitaminK-DependentCarboxylase 136
5.3.2 VitaminK-DependentProteinsinBloodClotting 139
5.3.3 OsteocalcinandMatrixGlaProtein 141
5.3.4 VitaminK-DependentProteinsinCellSignaling–Gas6 142
5.4 VitaminKDeficiency 142
5.4.1 VitaminKDeficiencyBleedinginInfancy 143
5.5 AssessmentofVitaminKNutritionalStatus 143
5.6 VitaminKRequirementsandReferenceIntakes 145
5.6.1 UpperLevelsofIntake 145
5.6.2 PharmacologicalUsesofVitaminK 146
6 VitaminB –Thiamin 148
1
6.1 ThiaminVitamersandAntagonists 148
6.2 MetabolismofThiamin 150
6.2.1 BiosynthesisofThiamin 153
6.3 MetabolicFunctionsofThiamin 153
6.3.1 ThiaminDiphosphateintheOxidativeDecarboxylation
ofOxoacids 154
6.3.1.1 RegulationofPyruvateDehydrogenaseActivity 155
6.3.1.2 Thiamin-ResponsivePyruvateDehydrogenase
Deficiency 156
6.3.1.3 2-OxoglutarateDehydrogenaseandtheγ-Aminobutyric
Acid(GABA)Shunt 156
6.3.1.4 Branched-ChainOxo-acidDecarboxylaseandMaple
SyrupUrineDisease 158
6.3.2 Transketolase 159
6.3.3 TheNeuronalFunctionofThiaminTriphosphate 159
6.4 ThiaminDeficiency 161
6.4.1 DryBeriberi 161
6.4.2 WetBeriberi 162
6.4.3 AcutePernicious(Fulminating)Beriberi–ShoshinBeriberi 162
6.4.4 TheWernicke–KorsakoffSyndrome 163
6.4.5 EffectsofThiaminDeficiencyonCarbohydrateMetabolism 164
6.4.6 EffectsofThiaminDeficiencyonNeurotransmitters 165
6.4.6.1 Acetylcholine 165
6.4.6.2 5-Hydroxytryptamine 165
6.4.7 ThiaminasesandThiaminAntagonists 166