Mass Spectrometry and Stable Isotopes in Nutritional and Pediatric Research

Henk Schierbeek, PhD is currently engaged as Associate Professor at the Academic Medical Centre (AMC) of the University of Amsterdam and is heading the mass spectrometry facility of the Mother and child division. Currently he is a board member of the Benelux Association of Stable Isotope Scientists (BASIS.)

• List of Contributors xviiIntroduction xxiList of Abbreviations xxiii1 Mass Spectrometry Techniques for In Vivo Stable Isotope Approaches 1Jean-Philippe Godin and Henk Schierbeek1.1 Introduction 11.2 Nomenclature for Light-Stable Isotope Changes 31.3 Mass Spectrometry Techniques 61.4 Choice of Mass Spectrometric Techniques and Applications to Measure Isotopic Enrichments in Metabolic Studies 261.5 Conclusion and Future Perspectives 30References 322 Stable Isotope Technology 45Dewi van Harskamp, Johannes B. van Goudoever, and Henk Schierbeek2.1 History 452.2 Definition 452.3 Safety 462.4 Stable Isotopes and Natural Abundances 472.5 Stable Isotope Selection 482.6 Single or Multiple Label Selection 492.7 Precursor Model 492.8 Simultaneous Infusion 492.9 Infusion Techniques 502.10 Steady State 522.11 Pool Selection 522.12 Pool Models 532.13 Flux: Synthesis and Breakdown 552.14 Nitrogen Balance 572.15 Doubly LabeledWater Method 572.16 Whole-body Protein Synthesis 582.17 Specific Protein Synthesis 582.18 Calculations 592.19 Considerations and Drawbacks of Isotopic Tracers 622.20 Conclusion 63References 633 Stable Isotopes in Nutritional and Pediatric Research 67Willemijn E. Corpeleijn and Johannes B. van Goudoever3.1 Introduction 673.2 Ethical Aspects 693.3 Applications of Stable Isotopes in Nutritional and Pediatric Research 703.4 Conclusion 78References 784 Early-Life Nutrition and Stable Isotope Techniques 81Stefanie M.P. Kouwenhoven and Marita deWaard4.1 Introduction 814.2 Breast Milk versus Infant Formula 814.3 Techniques to Monitor Milk Intake 824.4 Body Composition in Term and Preterm Infants 864.5 Amino Acid Requirement 864.6 Clinical Applications 874.7 Additional Applications 954.8 Discussion 984.9 Conclusion 994.10 Future Perspectives 99References 1005 Assessment of Amino Acid Requirement in Children Using Stable Isotopes 108Femke Maingay-de Groof and Henk Schierbeek5.1 Introduction 1085.2 Nutrient Needs and Definitions 1095.3 Methods to Determine Requirements 1115.4 Isotopic Tracer Methods 1125.5 Existing Methods to Determine Amino Acid Requirement for Neonates 1145.6 Use of the IAAO Method in the Pediatric Population 1155.7 Necessity for Performing the Study 1175.8 Biochemistry 1175.9 Available AnalyticalMethods 1205.10 Clinical Application 1205.11 Analysis and Calculations 1255.12 Results 1255.13 Statistical Analysis 1285.14 Discussion 1295.15 Conclusion 1315.16 Future Perspectives 132References 1326 Metabolism of Glutamine, Citrulline, and Arginine; Stable Isotopes Analyzing the Intestinal–Renal Axis 139Nikki Buijs, Saskia J.H. Brinkmann, Gerdien C. Ligthart-Melis, and Henk Schierbeek6.1 Introduction 1396.2 Biochemistry 1426.3 Isotopic Model 1466.4 Study Design 1486.5 Mass Spectrometry Methods 1516.6 Clinical Applications 1556.7 Calculations 1586.8 Discussion and Future Perspectives 161References 1677 Applications in Fat Absorption andMetabolism 175Dirk-Jan Reijngoud and Henkjan J. Verkade7.1 Introduction 1757.2 Biochemistry of Fat Absorption 1767.3 Isotope Model 1787.4 Study Design/Infusion Protocols 1797.5 Analytical Equipment 1817.6 Analytical Conditions 1817.7 Accuracy and Precision 1837.8 Calculations 1847.9 Clinical Applications 1877.10 Future Perspectives 191References 1938 Materno-Fetal Lipid Kinetics 197Elvira Larqué, Hans Demmelmair, and Berthold Koletzko8.1 Introduction 1978.2 Biochemistry of Placental Lipid Transport 1988.3 Investigation of Fatty Acid Metabolism Using Stable Isotopes 2008.4 Mass Spectrometry Methods 2028.5 Clinical Studies with Fatty Acids Labeled with Stable Isotopes in Healthy and Complicated Pregnancies 2038.6 Calculations 2078.7 Future Perspectives 209Acknowledgments 210References 2109 Stable Isotope Applications in Human In Vivo Placental and Fetal Research 213Chris H.P. van den Akker9.1 Introduction 2139.2 Investigation of FetalMetabolism Using Stable Isotopes 2149.3 Study Designs and Models 2159.4 Infusion Protocols and Clinical Applications 2169.5 Necessary Additional Clinical Parameters to be Analyzed 2189.6 Necessary Analytical Mass-Spectrometry Equipment and Analytical Conditions 2189.7 Calculations 2199.8 Future Perspectives 222References 22210 Obesity 225Margriet Veldhorst and Henk Schierbeek10.1 Introduction 22510.2 Singly and Doubly LabeledWater 22610.3 Substrate Oxidation 23710.4 Glucose Metabolism 23810.5 Fat Metabolism 23910.6 Protein Turnover 24210.7 Calculations 24610.8 Discussion and Future Perspectives 249References 25011 Inborn Errors of Metabolism 258Hidde H. Huidekoper, Frits A.Wijburg, and Ronald J.A.Wanders11.1 Introduction 25811.2 Stable Isotope Techniques 26011.3 Analytical Equipment and Methods 26711.4 Study Protocol: Quantifying Endogenous Galactose Production 26911.5 Calculations 27111.6 Discussion 27611.7 Future Perspectives 277References 27812 Renal Disease and Dialysis 284Gregorio P.Milani, Sander F. Garrelfs, and Michiel J.S. Oosterveld12.1 Introduction 28412.2 Total BodyWater and Its Distribution 28612.3 Protein Metabolism in Chronic Kidney Disease 29112.4 Dialysis – Metabolic Consequences and Nutrient Losses 29312.5 Primary Hyperoxalurias 29512.6 Clinical Applications 29812.7 Calculations 30312.8 Discussion 30812.9 Future Perspectives 310References 31013 Application in Oxidative Stress and Glutathione Metabolism in Preterm Infants 320Denise Rook and Henk Schierbeek13.1 Introduction 32013.2 Biochemistry/Model 32113.3 Guidelines and Safety Procedures 32313.4 Mass Spectrometry Methods 32313.5 Materials and Methods 32413.6 Clinical Application (A Practical Example of a Study Protocol) 32713.7 Calculations 32913.8 Discussion and Future Perspectives 330References 33114 Nutrient Digestion and Absorption During Intestinal Malfunction and Diseases 336Margot Fijlstra14.1 Introduction 33614.2 Clinical Application 340References 357Index 365