B Vitamins and Folate Chemistry, Analysis, Function and Effects 1 0 0 P F 4- 1 7 4 3 7 9 4 8 1 8 7 9 9/ 3 0 1 0. 1 oi: d g | or 2sc. 01s.r 2b er pu Octobhttp:// 7 n 1o n 2 o1 wnloaded October 20 Do1 3 n o d e h s bli u P View Online Food and Nutritional Components in Focus Series Editor: Professor Victor R. Preedy, School of Medicine, King’s College London, UK 1 0 0 P F 4- 1 7 4 3 7 49 Titles in the Series: 8 81 1: Vitamin A and Carotenoids: Chemistry, Analysis, Function and Effects 7 9/9 2: Caffeine: Chemistry, Analysis, Function and Effects 03 3: Dietary Sugars: Chemistry, Analysis, Function and Effects 1 0. 4: B Vitamins and Folate: Chemistry, Analysis, Function and Effects 1 oi: d g | or 2sc. 01s.r 2b er pu Octobhttp:// 7 n 1o n 2 o1 wnloaded October 20 Do1 3 n o d e h s bli u P How to obtain future titles on publication: A standing order plan is available for this series. A standing order will bring delivery of each new volume immediately on publication. For further information please contact: BookSalesDepartment,RoyalSocietyofChemistry,ThomasGrahamHouse, Science Park, Milton Road, Cambridge, CB4 0WF, UK Telephone: +44(0)1223 420066,Fax:+44(0)1223420247 Email:[email protected] Visit our website athttp://www.rsc.org/Shop/Books/ View Online B Vitamins and Folate Chemistry, Analysis, Function and Effects 1 0 0 P F 4- 1 7 34 Edited by 7 9 4 8 81 Victor R. Preedy 7 9 9/ School of Medicine, King’s College London, UK 3 0 1 0. 1 oi: d g | or 2sc. 01s.r 2b er pu Octobhttp:// 7 n 1o n 2 o1 wnloaded October 20 Do1 3 n o d e h s bli u P View Online 1 0 0 P F 4- 1 7 4 3 7 9 4 8 1 8 7 9 9/ 3 0 1 0. 1 oi: d g | or 2sc. 01s.r 2b er pu Octobhttp:// FoodandNutritionalComponentsinFocusNo.4 7 n n 12 o ISBN: 978-1-84973-369-4 o1 ISSN: 2045-1695 wnloaded October 20 AcataloguerecordforthisbookisavailablefromtheBritishLibrary Do1 rTheRoyalSocietyofChemistry2013 3 n d o Allrightsreserved e h s bli Apartfromfairdealingforthepurposesofresearchfornon-commercialpurposesorfor u P privatestudy,criticismorreview,aspermittedundertheCopyright,DesignsandPatents Act1988andtheCopyrightandRelatedRightsRegulations2003,thispublicationmaynot bereproduced,storedortransmitted,inanyformorbyanymeans,withouttheprior permissioninwritingofTheRoyalSocietyofChemistryorthecopyrightowner,orinthe caseofreproductioninaccordancewiththetermsoflicencesissuedbytheCopyright LicensingAgencyintheUK,orinaccordancewiththetermsofthelicencesissuedbythe appropriateReproductionRightsOrganizationoutsidetheUK.Enquiriesconcerning reproductionoutsidethetermsstatedhereshouldbesenttoTheRoyalSocietyof Chemistryattheaddressprintedonthispage. TheRSCisnotresponsibleforindividualopinionsexpressedinthiswork. PublishedbyTheRoyalSocietyofChemistry, ThomasGrahamHouse,SciencePark,MiltonRoad, CambridgeCB40WF,UK RegisteredCharityNumber207890 Forfurtherinformationseeourwebsiteatwww.rsc.org PrintedandboundinGreatBritainbyCPIGroup(UK)Ltd,Croydon,CR04YY,UK 5 0 0 P F 4- Preface 1 7 4 3 7 9 4 8 1 8 7 9 9/ 3 0 1 10. In the past three decades there have been major advances in our under- doi: standing of the chemistry and function of nutritional components. This has g | been enhanced by rapid developments in analytical techniques and instru- or 2sc. mentation. Chemists, food scientists and nutritionists are, however, separated 201bs.r by divergent skills and professional disciplines. Hitherto this transdisciplinary October http://pu divTidheeshearsiebseFeonoddiaffincduNltuttoribtiroindagleC. omponentsinFocusaimstocoverinasingle 7 n volumethechemistry,analysis,functionandeffectsofsinglecomponentsinthe 1o on 12 diet or its food matrix. Its aim is to embrace scientific disciplines so that wnloaded October 20 kinnfToohwrmeleadstegioreinebsbaseFecooaomnddesahnmadsoraNesumttrrueitacintouninraegldfuCflooarmnmpdaotan.penptlsicaibnleFtoocuhseaclothveirnsgtehneeralal.test Do1 3 B Vitamins and Folate has four major sections namely: n o d e h (cid:2) B Vitamins and Folate in Context s ubli (cid:2) Chemistry and Biochemistry P (cid:2) Analysis (cid:2) Function and Effects. Coverage includes B vitamins and folate in the context of a historical background, disease, cardiovascular effects and the importance of vitamins in biochemistryasillustratedbyasinglevitamin.Thereaftertherearechapterson the chemistry and biochemistry of thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate and cobalamin. Methodical aspects include characterization and assays of B vitamins and folate in foods of all kinds, dietary supplements, biological fluids and tissues. The techniques cover solid- phase extraction, spectrofluorimetry, mass spectrometry, HPLC, enzymatic assay, biosensor and chemiluminescence. In terms of function and effects or FoodandNutritionalComponentsinFocusNo.4 BVitaminsandFolate:Chemistry,Analysis,FunctionandEffects EditedbyVictorR.Preedy rTheRoyalSocietyofChemistry2013 PublishedbytheRoyalSocietyofChemistry,www.rsc.org v View Online vi Preface health and disease, there are both overviews and focused chapters covering suchtopicssuchascardiovasculardisease,stroke,cognitivedecline,dementia, epilepsy, micronutrient interventions, Wernicke’s encephalopathy, neuronal calcium, obesity, diabetes, gene expression, beta-oxidation, lipoprotein dis- 5 orders,pellagra,energymetabolism,immunity,kidneydiseaseandmanyother 0 P0 areas. F 4- Each chapter transcends the intellectual divide with a novel cohort of fea- 1 47 tures namely by containing: 3 7 9 4 18 (cid:2) an Abstract (appears in the eBook only) 8 97 (cid:2) Key Facts (areas of focus explained for the lay person) 9/ 3 (cid:2) Definitions of Words and Terms 0 1 0. (cid:2) Summary Points. 1 oi: d g | B Vitamins and Folate is designed for chemists, food scientist and nutri- or tionists, as well as health care workers and research scientists. Contributions 012s.rsc. are from leading national and international experts including contributions 2b er pu from world renowned institutions. Octobhttp:// Professor Victor R. Preedy, 7 n n 12 o King’s College London o1 wnloaded October 20 Do1 3 n o d e h s bli u P 7 0 0 P F 4- Contents 1 7 4 3 7 9 4 8 1 8 7 9 B Vitamins and Folate in Context 9/ 3 0 0.1 Chapter 1 Historical Context of Vitamin B 3 1 oi: Hideyuki Hayashi d g | or 1.1 Evidence for the Presence of Unidentified 012s.rsc. Factors Essential for Life 3 2b er pu 1.2 Establishment of the Concept of Vitamins 4 Octobhttp:// 11..34 RDeisscooluvetiroynthoaftVVitiatammininBs act as Coenzymes 66 7 n n 12 o 1.5 Influence on the Research into other Vitamins 8 o1 wnloaded October 20 111...678 MVAinitcaaremombiniiaaBla6NndutVriittiaomnainlsFactors and Vitamins 11209 Do1 1.9 Concluding Remarks 14 3 n Summary Points 15 o ed KeyFactsaboutBeriberiintheRusso-JapaneseWar(1905) 15 h blis List of Abbreviations 16 u P References 16 Chapter 2 B Vitamins and Disease 21 Jutta Dierkes and Ottar Nyga˚rd 2.1 Introduction 21 2.2 The Role of Different Study Types 22 2.3 Treatment of Deficiency or Supplementation without Reference to Vitamin Status 23 2.4 Mechanisms 24 2.5 Cardiovascular Disease 25 2.5.1 Folic acid, Vitamin B and Vitamin B 25 12 6 2.5.2 Niacin in Cholesterol Reduction 26 FoodandNutritionalComponentsinFocusNo.4 BVitaminsandFolate:Chemistry,Analysis,FunctionandEffects EditedbyVictorR.Preedy rTheRoyalSocietyofChemistry2013 PublishedbytheRoyalSocietyofChemistry,www.rsc.org vii View Online viii Contents 2.6 Cancer 27 2.7 Prevention of Age-related Cognitive Decline or Dementia 28 2.8 Renal Disease 28 7 2.9 Concluding Remarks 30 0 P0 Summary Points 30 F 4- List of Abbreviations 31 1 7 4 References 31 3 7 9 4 8 1 8 7 9/9 Chapter 3 Vitamins and Folate Fortification in the Context 3 0 of Cardiovascular Disease Prevention 35 1 10. Alexios S. Antonopoulos, Cheerag Shirodaria and doi: Charalambos Antoniades g | or 2sc. 3.1 Introduction 35 201bs.r 3.2 Homocysteinaemia as a Risk Factor for October http://pu A3.t2h.1erosMcleecrohsainsisms of Homocysteine-mediated 36 17 on Vascular Disease 36 n 2 o1 3.2.2 EpidemiologicalEvidenceonHomocysteineas Downloaded 1 October 20 3.3 CAanrydNioevaeadCscafuorldrairFoEvoafflasetcceutlsFaoorfrRtFiifisocklaicFtioAancct?iodr, B6 and B12: 3377 3 n 3.3.1 BVitaminsasHomocysteineLoweringAgents 37 o d 3.3.2 Effects on Proinflammatory Mechanisms 39 e h s 3.3.3 Effects on Endothelial Function 39 bli u 3.3.4 Further Mechanistic Insights in Human P Vessels 40 3.3.5 Effects on Atheroma Progression 40 3.4 Folate and B Vitamins in Cardiovascular Disease: Insights from Clinical Trials and Folate Fortification Programme 42 3.4.1 Homocysteine Lowering and Cardiovascular Disease Prevention 42 3.4.2 Criticism of Randomized Clinical Trials 43 3.4.3 Is Folate Fortification and B Vitamins Administration Safe? 46 3.5 Concluding Remarks 47 Summary Points 47 Key Facts about B Vitamins as Therapeutic Agents in Cardiovascular Disease 48 Definitions of Words and Terms 48 List of Abbreviations 49 References 50 View Online Contents ix Chapter 4 The Importance of Vitamins in Biochemistry and Disease as Illustrated by Thiamine Diphosphate (ThDP) Dependent Enzymes 55 Shinya Fushinobu and Ryuichiro Suzuki 7 0 P0 4.1 Reactions of ThDP-dependent Enzymes 55 F 4- 4.1.1 General Mechanism 55 1 47 4.1.2 Pyruvate-processing Enzymes 57 3 97 4.1.3 Transketolase and Phosphoketolase 59 4 18 4.2 Structures and Classification 61 8 97 4.2.1 Structures of TK and PK 61 9/ 3 4.2.2 Structures of Other ThDP-Dependent 0 1 0. Enzymes 62 1 oi: 4.2.3 Classification of ThDP-Dependent Enzyme d g | Families 62 or Summary Points 63 012s.rsc. Key Facts 64 2b er pu Key Facts about the History of Structural and Octobhttp:// FKuenycFtiaocntaslaSbtouudtieMs oetnabTohlDicPP-adtehpwenadyesnItnEvonlzvyinmges 64 7 n n 12 o ThDP-dependent Enzymes 64 o1 wnloaded October 20 DLRieesffitenoreiftniAocenbssborefvWiatoiordnssand Terms 666556 Do1 3 n o d he Chemistry and Biochemistry s bli Pu Chapter 5 The Chemistry, Biochemistry and Metabolism of Thiamin (Vitamin B) 71 1 Lucien Bettendorff 5.1 Introduction 71 5.2 Chemical Properties of Thiamin 72 5.3 Thiamin Biosynthesis and Degradation 77 5.4 Riboswitches 77 5.5 Thiamin Transport 78 5.5.1 Thiamin Transporters in Mammalian Cells 78 5.5.2 Mitochondrial Transport of Thiamin Diphosphate 79 5.6 Distribution of Thiamin Derivatives in Living Organisms 79 5.6.1 Occurrence of ThDP 80 5.6.2 Occurrence of ThTP 80 5.6.3 Occurrence of Adenylated Thiamin Derivatives 81 View Online x Contents 5.7 Metabolism of Thiamin Phosphates 81 5.7.1 Free and Bound ThDP Pools Coexist in the Same Cell 81 5.7.2 Synthesis of Thiamin Diphosphate 83 7 5.7.3 Synthesis of ThTP 84 0 P0 5.7.4 Synthesis of AThTP 84 F 4- 5.7.5 Hydrolysis of ThMP 84 1 47 5.7.6 Hydrolysis of ThDP 85 3 97 5.7.7 Hydrolysis of ThTP 85 4 18 5.7.8 Thiamin-binding Proteins 86 8 97 5.8 Concluding Remarks 87 9/ 3 Summary Points 87 0 1 0. Key Facts about Thiamin-related Diseases in Humans 88 1 oi: Definitions of Words and Terms 88 d g | List of Abbreviations 89 or References 89 2sc. 01s.r 2b er pu Chapter 6 Chemistry and Biochemistry of Riboflavin and Octobhttp:// Related Compounds 93 7 n Mariana C. Monteiro and Daniel Perrone 1o n 2 o1 wnloaded October 20 6.1 C66..h11e..12misSMtrtyroudoceftsuRroeifbaoDnfledagvrGianednaetrioanl ParnodpeSrttaiebsility in Foods 999533 Do1 3 6.2 Biochemistry of Riboflavin 97 n d o 6.2.1 Digestion, Bioavailability, Absorption and e h Transport 97 s bli 6.2.2 Metabolism, Storage and Excretion 100 u P 6.2.3 Biological Functions 101 6.2.4 Requirements and Intakes 101 Summary Points 103 Key Facts about Digestion and Absorption 103 Definitions of Words and Terms 104 List of Abbreviations 105 References 105 Chapter 7 The Chemistry and Biochemistry of Niacin (B ) 108 3 Asdrubal Aguilera-Me´ndez, Cynthia Ferna´ndez-Lainez, Isabel Ibarra-Gonza´lez and Cristina Fernandez-Mejia 7.1 Introduction 108 7.2 Niacin Chemistry 109 7.3 Niacin Daily Requirement, Food Sources and Niacin Deficiency 110 7.4 Factors and Diseases Affecting Niacin Requirement 110