Lipidomics: Comprehensive Mass Spectrometry of Lipids

Covers the area of lipidomics from fundamentals and theory to applications and methods

After years of development, the fundamentals and methodologies of lipidomics strategies have greatly advanced. The advancements and discoveries made in the field have been well–recognized in a great number of publications, special issues in a variety of prestigious journals, and several books edited by experts in the field. It is also clear that the progress of lipidomics has been accelerated by the development of modern mass spectrometry. Mass spectrometric analysis of lipids plays a key role in the discipline. However a systematic and detailed description of these fundamentals, technologies, advancements, and applications is still missing. This book is focused on the mass spectrometry of lipids that has occurred in these years.

The content of this book is classified into four sections: introduction, characterization, quantification, and application. The first part provides the fundamentals of lipids, lipidomics, and mass spectrometry. In the second section, pattern recognition for characterization of lipids is emphasized. Appropriate sampling, good practice of lipid extraction, addition of internal standards, practical methods for accurate quantification, data quality control, and others are the topics of the third section. The application of lipidomics strategies for biological and biomedical research is the last section of the book. 

Lipidomics: Comprehensive Mass Spectrometry of Lipids features:

Examples of a variety of diseases including metabolic syndrome, neurological and neurodegenerative diseases, and cancer Lipidomics in subcellular organelles and membrane fractions is also discussed to a great degree in this section. Large attention on practical quantification of Lipids in Lipidomics such as sample preparation; factors affecting accurate quantification; and data processing and interpretation Broad applications of Lipidomics Tools including for Health and Disease; Plant Lipidomics, and Lipidomics on Cellular Membranes

This monograph steps boldly into the area of lipidomics by providing important insights, information, and directions into how one can analyze lipids by mass spectrometry. This book very nicely engages these and more topics that are absolutely essential if one is to use this approach to further unravel and marvel at the mysteries of the living system.

Xianlin Han is a Professor in the Programs of Cardiovascular Metabolism and Integrative Metabolism at the Sanford Burnham Prebys Medical Discovery Institute. Prof. Han is one of the pioneers in lipidomics and the inventor of shotgun lipidomics. He has published over 180 peer–reviewed papers in journals and 16 invited book chapters with an H–index of 62. He holds 5 international patents. He is the associate editor of Lipids . Prof. Han serves as a member of the Editorial Board of numerous international journals including J. Lipid Res., Mol. Cell Biol. Lipids in Biochim. Biophys. Acta, Chem. Phys. Lipids, and Anal. Biochem.

 

Part I. INTRODUCTION

Chapter 1. Lipids and Lipidomics

1.1 Lipids

1.1.1 Definition

1.1.2 Classification

1.1.2.1 Lipid MAPS approach

1.1.2.2 Building block approach

1.1.2.2.1 Building block concept and classification

1.1.2.2.2 The significance of building block classification

1.2 Lipidomics

1.2.1 Definition

1.2.2 History of lipidomics

References

Chapter 2. Mass Spectrometry for Lipidomics

2.1 Ionization techniques

2.1.1 Electrospray ionization

2.1.1.1 Principle of electrospray ionization

2.1.1.2 Features of electrospray ionization for lipid analysis

2.1.1.3 Advent of ESI for lipid analysis: nanoESI and off–axis ion inlets

2.1.2 Matrix–assisted laser desorption/ionization

2.2 Mass analyzers

2.2.1 Quadrupole

2.2.2 Time–of–flight

2.2.3 Ion trap

2.3 Detector

2.4 Tandem mass spectrometry techniques

2.4.1 Product ion analysis

2.4.2 Neutral–loss scan

2.4.3 Precursor–ion scan

2.4.4 Selected reaction monitoring

2.4.5 Tandem mass spectrometry techniques are interwoven

2.5 Other recent advances in mass spectrometry for lipid analysis

2.5.1 Ion–mobility mass spectrometry

2.5.2 Desorption electrospray ionization

References

Chapter 3 Mass Spectrometry–based Lipidomics Approaches

3.1 Introduction

3.2 Shotgun lipidomics direct infusion–based approaches

3.2.1 Devices for direct infusion

3.2.2 Features of shotgun lipidomics

3.2.3 Shotgun lipidomics approaches

3.2.3.1 Tandem mass spectrometry–based shotgun lipidomics

3.2.3.2 High mass accuracy–based shotgun lipidomics

3.2.3.3 Multi–dimensional mass spectrometry–based shotgun lipidomics

3.2.4 Advantages and drawbacks

3.2.4.1 Tandem mass spectrometry–based shotgun lipidomics

3.2.4.2 High mass accuracy–based shotgun lipidomics

3.2.4.3 Multi–dimensional mass spectrometry–based shotgun lipidomics

3.3 LC–MS based approaches for lipidomics

3.3.1 General

3.3.1.1 Selected ion monitoring for LC–MS

3.3.1.2 Selected/multiple reaction monitoring for LC–MS

3.3.1.3 Data–dependent analysis after LC–MS

3.3.2 LC–MS based approaches

3.3.2.1 Normal–phase LC–MS based approaches

3.3.2.2 Reversed–phase LC–MS based approaches

3.3.2.3 Hydrophilic interaction LC–MS based approaches

3.3.2.4 Other LC–MS based approaches

3.3.3 Advantages and drawbacks

3.3.4 Identification of lipid species after LC–MS

3.4 MALDI–MS for lipidomics

3.4.1 General

3.4.2 Analysis of lipid extracts

3.4.3 In situ analysis of tissue lipids and MALDI–MS imaging

3.4.4 Advantages and drawbacks

3.4.5 Recent advances in MALDI–MS for lipidomics

3.4.5.1 Utilization of novel matrices

3.4.5.2 HPTLC–MADLI–MS

3.4.5.3 Matrix–free laser desorption/ionization approaches

References

Chapter 4. Variables in Mass Spectrometry for Lipidomics

4.1 Introduction

4.2 Variables in lipid extraction (i.e., multiplex extraction conditions)

4.2.1 The pH conditions of lipid extraction

4.2.2 Solvent polarity of lipid extraction

4.2.3 Intrinsic chemical properties of lipids

4.3 Variables in infusion solution

4.3.1 Polarity, composition, ion pairing, and others in the infusion solution

4.3.2 Variation of the level or composition of a modifier in the infusion solution

4.3.3 Lipid concentration in the infusion solution

4.4 Variables in ionization

4.4.1 Capillary temperature

4.4.2 Spray voltage

4.4.3 Injection/eluent flow rate

4.5 Variables in building–block monitoring with MS/MS scanning

4.5.1 Precursor–ion scanning of a fragment ion whose m/z serves as a variable

4.5.2 Neutral–loss scanning of a neutral fragment whose mass serves as a variable

4.5.3 Fragments associated with the building blocks are the variables in product–ion MS analysis

4.6 Variables in collision

4.6.1 Collision energy

4.6.2 Collision–gas pressure

4.6.3 Collision gas type

4.7 Variables in separation

4.7.1 Charge properties in intrasource separation

4.7.2 Elution time in LC separation

4.7.3 Matrix properties in selective ionization by MALDI

4.7.4 Drift time (or collision cross section) in ion–mobility separation

4.8 Conclusion

References

Chapter 5. Bioinformatics in Lipidomics

5.1 Introduction

5.2 Lipid libraries and databases

5.2.1 Lipid MAPS structure database

5.2.2 Building block concept–based theoretical databases

5.2.3 LipidBlast in silico tandem mass spectral library

5.2.4 METLIN database

5.2.5 Human Metabolome Database

5.2.6 LipidBANK database

5.3 Bioinformatics tools in automated lipid data processing

5.3.1 Spectral processing

5.3.2 Biostatistical analyses and visualization

5.3.3 Annotation for structure of lipid species

5.3.4 Software packages for common data processing

5.3.4.1 XCMC

5.3.4.2 MZmine

5.3.4.3 A practical approach for determination of mass spectral baselines

5.3.4.4 LipidView

5.3.4.5 Lipid Search

5.3.4.6 SimLipid

5.3.4.7 MultiQuant

5.3.4.8 Software packages for shotgun lipidomics

5.4 Bioinformatics for lipid network/pathway analysis and modeling

5.4.1 Reconstruction of lipid network/pathway

5.4.2 Simulation of lipidomics data for interpretation of biosynthesis pathways

5.4.3 Modeling of spatial distributions and biophysical context

5.5 Integration of omics

5.5.1 Integration of lipidomics with other omics

5.5.2 Lipidomics guides genomics analysis

References

Part II. CHARACTERIZATION OF LIPIDS

Chapter 6. Introduction

6.1 Structural characterization for lipid identification

6.2 Pattern recognition for lipid identification

6.2.1 Principles of pattern recognition

6.2.2 Examples

6.2.2.1 Choline lysoglycerophospholipid

6.2.2.2 Sphingomyelin

6.2.2.3 Triacylglycerol

6.2.3 Summary

References

Chapter 7. Fragmentation Patterns of Glycerophospholipids

7.1 Introduction

7.2 Choline glycerophospholipid

7.2.1 Positive ion mode

7.2.1.1 Protonated species

7.2.1.2 Alkaline adducts

7.2.2 Negative ion mode

7.3 Ethanolamine glycerophospholipid

7.3.1 Positive ion mode

7.3.1.1 Protonated species

7.3.1.2 Alkaline adducts

7.3.2 Negative ion mode

7.3.2.1 Deprotonated species

7.3.2.2 Derivatized species

7.4 Phosphatidylinositol and phosphatidylinositides

7.4.1 Positive ion mode

7.4.2 Negative ion mode

7.5 Phosphatidylserine

7.5.1 Positive ion mode

7.5.2 Negative ion mode

7.6 Phosphatidylglycerol

7.6.1 Positive ion mode

7.6.2 Negative ion mode

7.7 Phosphatidic acid

7.7.1 Positive ion mode

7.7.2 Negative ion mode

7.8 Cardiolipin

7.9 Lysoglycerophospholipids

7.9.1 Choline lysoglycerophospholipids

7.9.2 Ethanolamine lysoglycerophospholipids

7.9.3 Anionic lysoglycerophospholipids

7.10 Other glycerophospholipids

7.10.1 N–acyl phosphatidylethanolamine

7.10.2 N–acyl phosphatidylserine

7.10.3 Acyl phosphatidylglycerol

7.10.4 Bis(monoacylglycero)phosphate

7.10.5 Cyclic phosphatidic acid

References

Chapter 8. Fragmentation Patterns of Sphingolipids

8.1 Introduction

8.2 Ceramide

8.2.1 Positive ion mode

8.2.2 Negative ion mode

8.3 Sphingomyelin

8.3.1 Positive ion mode

8.3.2 Negative ion mode

8.4 Cerebroside

8.4.1 Positive ion mode

8.4.2 Negative ion mode

8.5 Sulfatide

8.6 Oligoglycosylceramide and gangliosides

8.7 Inositol phosphorylceramide

8.8 Sphingolipid metabolites

8.8.1 Sphingoid bases

8.8.2 Sphingoid–1–phosphate

8.8.3 Lysosphingomyelin

8.8.4 Psychosine

8.8.5 Ceramide–1–phosphate

References

Chapter 9. Fragmentation Patterns of Glycerolipids

9.1 Introduction

9.2 Monoglyceride

9.3 Diglyceride

9.4 Triglyceride

9.5 Hexosyl diacylglycerol

9.6 Other glycolipids

References

Chapter 10. Fragmentation Patterns of Fatty Acids and Modified Fatty Acids

10.1 Introduction

10.2 Non–esterified fatty acid

10.2.1 Underivatized non–esterified fatty acid

10.2.1.1 Positive–ion mode

10.2.1.2 Negative–ion mode

10.2.2 Derivatized non–esterified fatty acid

10.2.2.1 Off–line derivatization

10.2.2.2 On–line derivatization (Ozonolysis)

10.3 Modified fatty acid

10.4 Fatty acidomics

References

Chapter 11. Fragmentation Patterns of Other Bioactive Lipid Metabolites

11.1 Introduction

11.2 Acylcarnitine

11.3 Acyl–CoA

11.4 Endocannabinoids

11.4.1 N–Acyl ethanolamine

11.4.2 2–Acyl glycerol

11.4.3 N–Acyl amino acid

11.5 4–Hydroxalkenal

11.6 Chlorinated lipids

11.7 Sterols and oxysterols

11.8 Fatty acid–hydroxy fatty acids

References

Chapter 12. Imaging Mass Spectrometry of Lipids

12.1 Introduction

12.1.1 Samples suitable for MS imaging of lipids

12.1.2 Sample processing/preparation

12.1.3 Matrix application

12.1.3.1 Matrix application

12.1.3.2 Matrix application methods

12.1.4 Data processing

12.1.4.1 Biomap

12.1.4.2 FlexImaging

12.1.4.3 MALDI imaging team imaging computing system (MITICS)

12.1.4.4 Datacube Explorer

12.1.4.5 imzML

12.2 MALDI–MS imaging

12.3 Secondary ion mass spectrometry imaging

12.4 DESI–MS imaging

12.5 Ion–mobility imaging

12.6 Advantages and drawbacks of imaging mass spectrometry for analysis of lipids

12.6.1 Advantages

12.6.2 Limitations

References

Part III. QUANTIFICATION OF LIPIDS IN LIPIDOMICS

Chapter 13. Sample Preparation

13.1 Introduction

13.2 Sampling, storage, and related concerns

13.2.1 Sampling

13.2.2 Sample storage prior to extraction

13.2.3 Minimizing autoxidation

13.3 Principles and methods of lipid extraction

13.3.1 Principles of lipid extraction

13.3.2 Internal standards

13.3.3 Lipid extraction methods

13.3.3.1 Folch extraction

13.3.3.2 Bligh–Dyer extraction

13.3.3.3 MTBE extraction

13.3.3.3 BUME extraction

13.3.3.5 Extraction of plant samples

13.3.3.6 Special cases

13.3.4 Contaminants and artifacts in extraction

13.3.5 Storage of lipid extracts

References

Chapter 14. Quantification of Individual Lipid Species in Lipidomics

14.1 Introduction

14.2 Principles of quantifying lipid species by mass spectrometry

14.3 Methods for quantification in lipidomics

14.3.1 Tandem mass spectrometry–based method

14.3.2 Two–step quantification approach used in MDMS–SL

14.3.3 Selected ion monitoring method

14.3.4 Selected–reaction monitoring method

14.3.5 High mass accuracy mass spectrometry approach

References

Chapter 15. Factors Affecting Accurate Quantification of Lipids

15.1 Introduction

15.2 Lipid aggregation

15.3 Linear dynamic range of quantification

15.4 Nuts and bolts of tandem mass spectrometry for quantification of lipids

15.5 Ion suppression

15.6 Spectral baseline

15.7 The effects of isotopes

15.8 Minimal number of internal standards for quantification

15.9 In–source fragmentation

15.10 Quality of solvents

15.11 Miscellaneous in quantitative analysis of lipids

References

Chapter 16. Data Quality Control and Interpretation

16.1 Introduction

16.2 Data quality control

16.3 Recognition of lipid metabolism pathways for data interpretation

16.3.1 Sphingolipid metabolic pathway network

16.3.2 Network of glycerophospholipid biosynthesis pathways

16.3.3 Glycerolipid metabolism

16.3.4 Inter–relationship between different lipid categories

16.4 Recognition of lipid functions for data interpretation

16.5.1 Lipids serve as cellular membrane components

16.5.2 Lipids serve as cellular energy depots

16.5.3 Lipids serve as signaling molecules

16.5.4 Lipids play other cellular roles

16.5 Recognizing the complication of sample inhomogeneity and cellular compartments in data interpretation

16.6 Integration of omics for data supporting

References

Part IV. APPLICATIONS OF LIPIDOMICS IN BIOMEDICAL AND BIOLOGICAL RESEARCH

Chapter 17. Lipidomics for Health and Disease

17.1 Introduction

17.2 Diabetes and obesity

17.3 Cardiovascular diseases

17.4 Non–alcohol fatty liver disease

17.5 Alzheimer s disease

17.6 Psychosis

17.7 Cancer

17.8 Lipidomics in nutrition and food

17.8.1 Lipidomics in determination of the effects of specific diets or challenge tests

17.8.2 Lipidomics to control food quality

References

Chapter 18. Plant Lipidomics

18.1 Introduction

18.2 Characterization of lipids special to plant lipidome

18.2.1 Galactolipids

18.2.2 Sphingolipids

18.2.3 Sterols and derivatives

18.2.4 Sulfolipids

18.2.5 Lipid A and intermediates

18.3 Lipidomics for plant biology

18.3.1 Stress–induced changes of plant lipidomes

18.3.1.1 Lipid alterations in plants induced by temperature changes

18.3.1.2 Wounding–induced alterations in plastidic lipids

18.3.1.3 Phosphorus deficiency–resulted changes of glycerophospholipids and galactolipids

18.3.2 Changes of plant lipidomes during development

18.3.2.1 Alterations in lipids during development of cotton fibers

18.3.2.2 Changes of lipids during potato tuber aging and sprouting

18.3.3 Characterization of gene function by lipidomics

18.3.3.1 Role of fatty acid desaturases and DHAP reductase in systemic acquired resistance

18.3.3.2 Roles of phospholipases in response to freezing

18.3.3.3 Role of PLD in phosphorus deficiency–induced lipid changes

18.3.4 Lipidomics facilitates improvement of genetically modified food quality

References

Chapter 19. Lipidomics on Yeast and Mycobacterium

19.1 Introduction

19.2 Yeast lipidomics

19.2.1 Protocol for analysis of yeast lipidomes by mass spectrometry

19.2.2 Quantitative analysis of yeast lipidomes

19.2.3 Comparative lipidomics studies on different yeast strains

19.2.4 Lipidomics of yeast for lipid biosynthesis and function

19.2.5 Determining the effects of growth conditions on yeast lipidomes

19.3 Mycobacterium lipidomics

References

Chapter 20. Lipidomics on Cell Organelle and Subcellular Membranes

20.1 Introduction

20.2 Golgi

20.3 Lipid droplets

20.4 Lipid rafts

20.5 Mitochondrion

20.6 Nucleus

20.7 Conclusion

References

Abbreviation

Index