Metabolomics, metabonomics and metabolite profiling

Metabolomics, Metabonomics and Metabolite Profiling......Page 1
Preface......Page 5
Contents......Page 6
1.2.1 Principles......Page 13
1.2.2 Ionisation......Page 14
1.2.3 Mass Analysers......Page 26
1.2.4 Gas Chromatography/Mass Spectrometry (GC-MS)......Page 34
1.2.5 Tandem Mass Spectrometry (MS/MS)......Page 38
1.2.6 Liquid Chromatography–Mass Spectrometry(LC-MS)......Page 39
1.3 Future Perspectives......Page 41
References......Page 43
2.1 Introduction......Page 56
2.2.1 Sample Preparation......Page 58
2.2.21 D NMR Methods......Page 59
2.2.32 D NMR Methods......Page 63
2.3.1 NMR Fingerprinting......Page 68
2.3.3 NMR Profiling......Page 75
2.3.4 Reporting Requirements for NMR Metabolomics......Page 77
2.4 Conclusions and Future Developments......Page 78
References......Page 79
3.1 Introduction......Page 83
3.2.3 Oxysterols......Page 90
3.2.4 Neurosterols......Page 97
3.2.5 Biological Activity of Oxysterols......Page 98
3.3 Analysis by Mass Spectrometry......Page 99
3.3.1 GC-MS Analysis......Page 100
3.3.2 LC-MS Analysis......Page 102
3.4 Metabolite Profiling in Brain: Neurosteroids and Neurosterols......Page 108
3.5 Linking Proteomics with Lipidomics......Page 113
Appendix......Page 118
References......Page 120
4.1 General Overview of Lipidomic Characterisation of Membrane Function......Page 128
4.2 Phospholipid Structures......Page 129
4.3 Electrospray Ionisation Mass Spectrometry of Phospholipids......Page 130
4.4 Phospholipid Metabolism......Page 133
4.5 Phospholipids of Lung Surfactant......Page 134
4.5.1 Lung Structure and Surfactant Function......Page 135
4.5.2 ESI/MS Analysis of Lung Surfactant Phospholipid......Page 137
References......Page 143
5.1 Introduction......Page 146
5.2.1 Multiplexed Extractions......Page 149
5.2.2 Intrasource Separation......Page 150
5.2.3 Identification of Lipid Molecular Species by Multi-dimensional Mass Spectrometry and Array Analysis......Page 151
5.2.5 Analysis in the Low Concentration Regime by Shotgun Lipidomics......Page 153
5.3 The Chemical Mechanisms Underlying Intrasource Separation......Page 154
5.4 An Enhanced Shotgun Lipidomics for Cardiolipin Analysis......Page 157
5.5 Derivatization as an Additional Dimension of Multi-dimension Mass Spectrometry in Shotgun Lipidomics......Page 162
5.5.1 Derivatization of Phosphoethanolaminecontaining Lipid Molecular Species for Shotgun Lipidomics......Page 164
5.5.2 Derivatization of Cholesterol with Methoxyacetic Acid for Quantitation by Shotgun Lipidomics......Page 168
References......Page 170
6.1.1 Neutral Lipid Analysis and Lipidomics......Page 173
6.2.1 Overview......Page 174
6.2.2 Electron Ionization (EI)......Page 176
6.2.3 Negative-ion Chemical Ionization (NCI)......Page 177
6.2.4 Electrospray Ionization/Tandem Mass Spectrometry......Page 178
6.2.5 Atmospheric Pressure Chemical Ionization......Page 185
6.3 Cholesterol Esters......Page 189
6.3.1 Electron Ionization......Page 191
6.3.3 Electrospray Ionization......Page 192
6.4 Wax Esters......Page 193
6.4.1 Electron Ionization......Page 195
6.4.2 Electrospray and Desorption Ionization......Page 200
References......Page 201
7.1 Introduction......Page 207
7.2.1 Classification......Page 208
7.2.2 Nomenclature......Page 211
7.3 Lipid Molecular Databases......Page 212
7.4 Lipid-associated Protein/Gene Databases......Page 214
7.5 Lipid-associated Pathways and Networks......Page 215
7.6.1 Data Collection......Page 216
7.6.2 Standards Libraries......Page 217
7.6.3 MS Prediction Tools......Page 218
7.6.4 Automated Structure Drawing......Page 219
References......Page 220
8.1 Introduction......Page 222
8.2.1 Sampling and Extraction......Page 224
8.2.3 Analytical Methods......Page 225
8.2.4 Data Analysis......Page 229
8.3 Metabolic Disorders of Carbohydrate Metabolism......Page 230
8.3.1 Sampling and Extraction......Page 231
8.3.2 Sample Handling and Derivatisation......Page 232
8.3.3 Analytical Methods......Page 233
8.4 Glucuronidated Metabolites as Biomarkers for Drug and Alcohol Abuse......Page 236
8.4.1 Sampling and Extraction......Page 237
8.4.3 Analytical Methods......Page 238
8.5 Conclusions......Page 242
References......Page 243
9.1 Introduction......Page 246
9.2.1 Instrumentation for MALDI-MSI......Page 247
9.2.2 Sample Preparation Procedures......Page 250
9.3.2 MALDI-MSI in the Study of Drug/Xenobiotic Distribution......Page 252
9.3.3 MALDI-MSI and Phospholipids......Page 256
9.3.4 MALDI-MSI and Metabonomics......Page 258
9.4 Data Handling and Data Interpretation Issues......Page 261
References......Page 263
10.1 Introduction......Page 266
10.2.1 General Considerations......Page 267
10.2.2 Sample Preparation......Page 268
10.2.3 GC/MS......Page 269
10.2.4 LC/MS......Page 271
10.3.1 Phenotyping Plants Using Metabolomics......Page 273
10.3.2 Genetic Metabolomics: Identification of Metabolic QTLs......Page 276
10.3.3 Plant Metabolomics and Gene Identification......Page 277
10.4 Conclusions and Future Directions......Page 280
References......Page 281
11.1 Introduction......Page 285
11.1.1 Data Extraction-Generating Variables......Page 286
11.1.2 Data Pre-treatment......Page 290
11.2 Data Mining......Page 291
11.2.1 Multivariate Data Mining......Page 292
11.2.2 Exploratory Data Mining......Page 295
11.2.3 Databases......Page 296
References......Page 300
12.1 Introduction......Page 307
12.2 Biological Fluids as a Window on the Global 'System'......Page 309
12.3 Examples of the Use of Metabonomics in Normal and Disease Models......Page 310
12.4 The Microbiome-an Integral Part of the Global System......Page 315
12.5 Pharmaco-metabonomics......Page 318
12.6 Combining Omics......Page 319
References......Page 326
Subject Index......Page 329