Metabolomics, Metabonomics and Metabolite Profiling (Rsc Bimolecular Sciences) - Hardcover

Hardcover

ISBN 10: 0854042997 ISBN 13: 9780854042999

Verlag: Royal Society of Chemistry, 2007

Inhaltsangabe

The completion of gene sequencing has resulted in an intensified investigation of the proteome and metabolome. Metabolite profiling methods used for disease diagnosis have been expanded with the advent of new technology and are being applied extensively in the quest for the discovery of new markers for diseases. In this comprehensive resource, the Editor draws together experts from the field and provides an insightful introduction into the technology and methodology. Metabolomics, Metabonomics And Metabolite Profiling covers a broad range of topics including: *Mass spectrometry and NMR in metabolite profiling *Current applications of metabolite profiling for disease diagnosis *Studies of specific metabolite classes *Plant metabolites *Metabolite data mining *Global systems biology This book is a must have, up-to-date, reference which will appeal to academics, students, technicians and professionals working in, or joining this field.

Über diesen Titel

Über die Autorin bzw. den Autor

Robert C Murphy graduated from Massachusetts Institute of Technology with a PhD in chemistry and he is currently a University Distinguished Professor at the University of Colorado. He has worked in the area of mass spectrometry and eicosanoid biochemistry for approximately 40 years with much of his research activities centered on the use of mass spectrometry to studies of arachidonic acid biochemistry and formation of the biologically active leukotriene mediators. His interests also include the structural characterizaton of bioactive lipid products derived from the reaction of reactive oxygen species with cellular lipids. Over 400 peer-reviewed papers in scientific journals and several books concerning mass spectrometry of lipids have been authored by him.

Von der hinteren Coverseite

The completion of gene sequencing has resulted in an intensified investigation of the proteome and metabolome. Metabolite profiling methods used for disease diagnosis have been expanded with the advent of new technology and are being applied extensively in the quest for the discovery of new markers for diseases. In this comprehensive resource the Editor draws together experts from the field and provides an insightful introduction into the technology and methodology. Metabolomics, Metabonomics and Metabolite Profiling covers a broad range of topics including: "Mass spectrometry and NMR in metabolite profiling "Current applications of metabolite profiling for disease diagnosis "Studies of specific metabolite classes "Plant metabolites "Metabolite data mining "Global systems biology This book is a must have, up-to-date, reference which will appeal to academics, students, technicians and professionals working in, or joining this field. William J. Griffiths xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx Author Bio?????

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Metabolomics, Metabonomics and Metabolite Profiling

By William J. Griffiths

The Royal Society of Chemistry

Copyright © 2008 The Royal Society of Chemistry
All rights reserved.

ISBN: 978-0-85404-299-9

Contents

Chapter 1 Mass Spectrometry for Metabolite Identification Yuqin Wang and William J. Griffiths, 
Chapter 2 1D and 2D NMR Spectroscopy: From Metabolic Fingerprinting to Profiling Mark R. Viant, Christian Ludwig and Ulrich L. Günther, 
Chapter 3 Steroids, Sterols and the Nervous System Yuqin Wang and William J. Griffiths, 
Chapter 4 Phospholipid Profiling Anthony D. Postle, 
Chapter 5 New Developments in Multi-dimensional Mass Spectrometry Based Shotgun Lipidomics Xianlin Han and Richard W. Gross, 
Chapter 6 Neutral Lipidomics and Mass Spectrometry Robert C. Murphy, Mark Fitzgerald and Robert M. Barkley, 
Chapter 7 Bioinformatics of Lipids Eoin Fahy, 
Chapter 8 Mass Spectrometry in Glycobiology João Rodrigues, Carla Antonio, Sarah Robinson and Jane Thomas-Oates, 
Chapter 9 Matrix Assisted Laser Desorption Ionisation Mass Spectrometric Imaging – Principles and Applications Caroline J. Earnshaw, Sally J. Atkinson, Michael Burrell and Malcolm R. Clench, 
Chapter 10 Plant Metabolomics Thomas Moritz and Annika I. Johansson, 
Chapter 11 Data Mining for Metabolomics Anders Nordström, 
Chapter 12 Metabonomics and Global Systems Biology Ian D Wilson and Jeremy K. Nicholson, 
Subject Index, 317, 

CHAPTER 1

Mass Spectrometry for Metabolite Identification

YUQIN WANG AND WILLIAM J. GRIFFITHS

The School of Pharmacy, University of London, 29–39 Brunswick Square, London WC1N 1AX, UK

1.1 Introduction

Mass spectrometry (MS) and nuclear magnetic resonance (NMR) constitute the two major pillars upon which the disciplines of metabolomics and metabolite profiling are built. Both these techniques have their advantages and disadvantages, but the fundamental difference in the nature of their spectroscopy means that they provide complementary information to the analytical scientist. NMR spectroscopy is discussed in detail in Chapter 2, while this chapter will concentrate on mass spectrometry and associated methodologies appropriate in metabolomics research. The principles of mass spectrometry will be described and examples of metabolite analysis given. As the range of metabolite structures present in biology (almost) exceeds the imagination, we will take many examples from the class of biomolecules that we have been most intimately involved with, i.e. sterols and steroids. However, many of the references quoted are equally applicable to other area of metabolite profiling and metabolomics.

1.2 Mass Spectrometry

1.2.1 Principles

Simplistically, a mass spectrometer consists of an ion source, a mass analyser, a detector and a data system (Figure 1.1). Sample molecules are admitted to the ion source, where they become ionised. The ions, which are now in the gas phase, are separated according to their mass-to-charge ratio (m/z) in the mass analyser and are then detected. The resulting signals are transmitted to the data system and a plot of ion abundance against m/z corresponds to a mass spectrum. In many cases, a separating inlet device precedes the ion source, so that complex mixtures can be separated prior to admission to the mass spectrometer. Today, the separating inlet device is usually either a capillary gas chromatography (GC) column or a high-performance liquid chromatography (HPLC) column, although capillary electrophoresis and thin-layer chromatography can be interfaced with mass spectrometry.

For metabolite analysis a number of different types of ionisation methods are used to generate gas-phase ions and these include: electron ionisation (EI), chemical ionisation (CI), electrospray (ES), atmospheric pressure chemical ionisation (APCI), atmospheric pressure photoionisation (APPI), and the recently introduced, desorption electrospray ionisation (DESI) technique. Other ionisation techniques used, but to a lesser extent, are liquid secondary ion mass spectrometry (LSIMS) and fast atom bombardment (FAB), or for more specific applications, matrix-assisted laser desorption/ionisation (MALDI) (see Chapter 9) and desorption ionisation on silicon (DIOS). The most widely used ionisation modes are discussed below, as are the chromatographic devices to which they are interfaced.

1.2.2 Ionisation

1.2.2.1 Electron Ionisation (EI) and Chemical Ionisation (CI)

Historically, the most important method of ionisation of small biomolecules (< ~500 Da) is EI. The effluent from a GC column is readily transferred to an EI source, thereby allowing the combination of the high separating power of a GC column with mass analysis. EI involves the bombardment of gas-phase sample molecules (M) with high-energy electrons (e-), usually of 70 eV energy; the result is the generation of [M]+• ions which are usually radical cations, and thermal energy free electrons (e-) (eqn 1).

[FORMULA NOT REPRODUCIBLE IN ASCII] (1)

In many cases the molecular ions, [M]+•, are unstable and fragment to generate more stable products (eqn 2).

[FORMULA NOT REPRODUCIBLE IN ASCII] (2)

Fragmentation upon EI can be seen as both advantageous and disadvantageous. On the plus side, the fragmentation pattern resulting from decomposition of a molecular ion can provide structural information, allowing its identification. On the negative side, however, fragmentation may be so extensive that the molecular ion may not be observed, and thus the molecular weight of the compound of interest not determined. EI can be used to generate either positive ions [M]+•or negative ions [M]+-. Negative ions are generated via an electron capture event, which involves the capture of secondary low-energy electrons generated by ionisation of a bath gas (e.g. Ar, N2) (eqn 3).

[FORMULA NOT REPRODUCIBLE IN ASCII] (3a)

[FORMULA NOT REPRODUCIBLE IN ASCII] (3b)

A prerequisite of EI is that the sample to be ionised must be in the gas phase; this is also true for GC and has led to the extensive development of derivatisation chemistry to allow the vaporisation of many small biomolecules without their decomposition.

CI is a close relative of EI. It differs in that analyte ionisation is achieved via proton attachment rather than electron ejection (positive ion). In CI the ion source contains a reagent gas, often methane, which becomes ionised by EI and acts as a proton donor to the analyte (eqn 4).

[FORMULA NOT REPRODUCIBLE IN ASCII] (4a)

[FORMULA NOT REPRODUCIBLE IN ASCII] (4b)

[FORMULA NOT REPRODUCIBLE IN ASCII] (4c)

The resulting ion, [M + H]+, is an even-electron protonated molecule, which is more stable than the equivalent odd-electron molecular ion, [M] +•, formed by EI, and thus fragments to only a minor extent.

Electron-capture negative ionisation (ECNI), also called electron-capture negative chemical ionisation (EC-NCI), exploits the electron capturing properties of groups with high electron affinities (eqn 5). The method often utilises fluori-nated agents in the preparation of volatile derivatives with high electron affinities. For example, trifluoroacetic, pentafluoropropionic or heptafluorobutyric anhydrides can be used to prepare acyl derivatives of amines and hydroxyl groups, perfluorinated alcohols can be used to generate esters of carboxylic acids, while carbonyl groups can be converted to oximes which can then be converted to...

Details zur Ausgabe

• Verlag: Royal Society of Chemistry
• Erscheinungsdatum: 2007
• Sprache: Englisch
• ISBN 10: 0854042997
• ISBN 13: 9780854042999
• Einband: Gebundene Ausgabe
• Anzahl der Seiten: 323
• Herausgeber: Griffiths William J.
• Kontakt zum Hersteller: Nicht verfügbar
• Verantwortliche Person: Nicht verfügbar