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 xvii

Introduction xxi

List of Abbreviations xxiii

1 Mass Spectrometry Techniques for In Vivo Stable Isotope Approaches 1
Jean-Philippe Godin and Henk Schierbeek

1.1 Introduction 1

1.2 Nomenclature for Light-Stable Isotope Changes 3

1.3 Mass Spectrometry Techniques 6

1.4 Choice of Mass Spectrometric Techniques and Applications to Measure Isotopic Enrichments in Metabolic Studies 26

1.5 Conclusion and Future Perspectives 30

References 32

2 Stable Isotope Technology 45
Dewi van Harskamp, Johannes B. van Goudoever, and Henk Schierbeek

2.1 History 45

2.2 Definition 45

2.3 Safety 46

2.4 Stable Isotopes and Natural Abundances 47

2.5 Stable Isotope Selection 48

2.6 Single or Multiple Label Selection 49

2.7 Precursor Model 49

2.8 Simultaneous Infusion 49

2.9 Infusion Techniques 50

2.10 Steady State 52

2.11 Pool Selection 52

2.12 Pool Models 53

2.13 Flux: Synthesis and Breakdown 55

2.14 Nitrogen Balance 57

2.15 Doubly LabeledWater Method 57

2.16 Whole-body Protein Synthesis 58

2.17 Specific Protein Synthesis 58

2.18 Calculations 59

2.19 Considerations and Drawbacks of Isotopic Tracers 62

2.20 Conclusion 63

References 63

3 Stable Isotopes in Nutritional and Pediatric Research 67
Willemijn E. Corpeleijn and Johannes B. van Goudoever

3.1 Introduction 67

3.2 Ethical Aspects 69

3.3 Applications of Stable Isotopes in Nutritional and Pediatric Research 70

3.4 Conclusion 78

References 78

4 Early-Life Nutrition and Stable Isotope Techniques 81
Stefanie M.P. Kouwenhoven and Marita deWaard

4.1 Introduction 81

4.2 Breast Milk versus Infant Formula 81

4.3 Techniques to Monitor Milk Intake 82

4.4 Body Composition in Term and Preterm Infants 86

4.5 Amino Acid Requirement 86

4.6 Clinical Applications 87

4.7 Additional Applications 95

4.8 Discussion 98

4.9 Conclusion 99

4.10 Future Perspectives 99

References 100

5 Assessment of Amino Acid Requirement in Children Using Stable Isotopes 108
Femke Maingay-de Groof and Henk Schierbeek

5.1 Introduction 108

5.2 Nutrient Needs and Definitions 109

5.3 Methods to Determine Requirements 111

5.4 Isotopic Tracer Methods 112

5.5 Existing Methods to Determine Amino Acid Requirement for Neonates 114

5.6 Use of the IAAO Method in the Pediatric Population 115

5.7 Necessity for Performing the Study 117

5.8 Biochemistry 117

5.9 Available AnalyticalMethods 120

5.10 Clinical Application 120

5.11 Analysis and Calculations 125

5.12 Results 125

5.13 Statistical Analysis 128

5.14 Discussion 129

5.15 Conclusion 131

5.16 Future Perspectives 132

References 132

6 Metabolism of Glutamine, Citrulline, and Arginine; Stable Isotopes Analyzing the Intestinal–Renal Axis 139
Nikki Buijs, Saskia J.H. Brinkmann, Gerdien C. Ligthart-Melis, and Henk Schierbeek

6.1 Introduction 139

6.2 Biochemistry 142

6.3 Isotopic Model 146

6.4 Study Design 148

6.5 Mass Spectrometry Methods 151

6.6 Clinical Applications 155

6.7 Calculations 158

6.8 Discussion and Future Perspectives 161

References 167

7 Applications in Fat Absorption andMetabolism 175
Dirk-Jan Reijngoud and Henkjan J. Verkade

7.1 Introduction 175

7.2 Biochemistry of Fat Absorption 176

7.3 Isotope Model 178

7.4 Study Design/Infusion Protocols 179

7.5 Analytical Equipment 181

7.6 Analytical Conditions 181

7.7 Accuracy and Precision 183

7.8 Calculations 184

7.9 Clinical Applications 187

7.10 Future Perspectives 191

References 193

8 Materno-Fetal Lipid Kinetics 197
Elvira Larqué, Hans Demmelmair, and Berthold Koletzko

8.1 Introduction 197

8.2 Biochemistry of Placental Lipid Transport 198

8.3 Investigation of Fatty Acid Metabolism Using Stable Isotopes 200

8.4 Mass Spectrometry Methods 202

8.5 Clinical Studies with Fatty Acids Labeled with Stable Isotopes in Healthy and Complicated Pregnancies 203

8.6 Calculations 207

8.7 Future Perspectives 209

Acknowledgments 210

References 210

9 Stable Isotope Applications in Human In Vivo Placental and Fetal Research 213
Chris H.P. van den Akker

9.1 Introduction 213

9.2 Investigation of FetalMetabolism Using Stable Isotopes 214

9.3 Study Designs and Models 215

9.4 Infusion Protocols and Clinical Applications 216

9.5 Necessary Additional Clinical Parameters to be Analyzed 218

9.6 Necessary Analytical Mass-Spectrometry Equipment and Analytical Conditions 218

9.7 Calculations 219

9.8 Future Perspectives 222

References 222

10 Obesity 225
Margriet Veldhorst and Henk Schierbeek

10.1 Introduction 225

10.2 Singly and Doubly LabeledWater 226

10.3 Substrate Oxidation 237

10.4 Glucose Metabolism 238

10.5 Fat Metabolism 239

10.6 Protein Turnover 242

10.7 Calculations 246

10.8 Discussion and Future Perspectives 249

References 250

11 Inborn Errors of Metabolism 258
Hidde H. Huidekoper, Frits A.Wijburg, and Ronald J.A.Wanders

11.1 Introduction 258

11.2 Stable Isotope Techniques 260

11.3 Analytical Equipment and Methods 267

11.4 Study Protocol: Quantifying Endogenous Galactose Production 269

11.5 Calculations 271

11.6 Discussion 276

11.7 Future Perspectives 277

References 278

12 Renal Disease and Dialysis 284
Gregorio P.Milani, Sander F. Garrelfs, and Michiel J.S. Oosterveld

12.1 Introduction 284

12.2 Total BodyWater and Its Distribution 286

12.3 Protein Metabolism in Chronic Kidney Disease 291

12.4 Dialysis – Metabolic Consequences and Nutrient Losses 293

12.5 Primary Hyperoxalurias 295

12.6 Clinical Applications 298

12.7 Calculations 303

12.8 Discussion 308

12.9 Future Perspectives 310

References 310

13 Application in Oxidative Stress and Glutathione Metabolism in Preterm Infants 320
Denise Rook and Henk Schierbeek

13.1 Introduction 320

13.2 Biochemistry/Model 321

13.3 Guidelines and Safety Procedures 323

13.4 Mass Spectrometry Methods 323

13.5 Materials and Methods 324

13.6 Clinical Application (A Practical Example of a Study Protocol) 327

13.7 Calculations 329

13.8 Discussion and Future Perspectives 330

References 331

14 Nutrient Digestion and Absorption During Intestinal Malfunction and Diseases 336
Margot Fijlstra

14.1 Introduction 336

14.2 Clinical Application 340

References 357

Index 365