New Frontiers for Mass Spectrometry in Lipidomics, Part I - - Chromatography Online
New Frontiers for Mass Spectrometry in Lipidomics, Part I


LCGC North America
Volume 30, Issue 2, pp. 120-133

This two-part column explains the evolution of lipids analysis, current approaches such as targeted and untargeted lipidomics, and the variety of techniques involved, including sample preparation, separations, and, of course, mass spectrometry.

The study of lipid biology is undergoing a remarkable, technology-driven transformation that most notably involves mass spectrometry (MS) and its ancillary techniques, such as liquid chromatography (LC) and ionization sources. Greater investment inflows and a surge of activity, especially in the field of drug and biomarker discovery, is fueling the growth of global lipid analysis — lipidomics — making it a standard research tool in academic, pharmaceutical, and biotechnology sectors. Additional areas of interest in lipidomics include plant, microbial, and nutritional research.

Why Lipids?

Lipids are absolutely essential for life, playing diverse and important roles in nutrition and health. Alterations in lipid metabolites are associated with various human diseases including obesity, heart disease, and diabetes mellitus (1,2). The ability to profile the lipid composition of biological samples is important in disease diagnosis and drug discovery, attracting strong social and economic interests. For example, the discovery that cholesterol and triglycerides are linked to heart disease affected clinical testing, as well as drug, food, and lifestyle enterprises. Indeed, for the last 50 years, we experienced a lipid phobia, the emblematic manifestations of which are readily apparent in the many food labels advertising "low fat" and "low cholesterol." Cholesterol-lowering agents, such as statins like atorvastatin (Lipitor, from Pfizer, New York, New York), are among the most successful drug classes, accounting for $21.5 billion a year market in the United States. Other commonplace drugs, such as nonsteroidal anti-inflammatory drugs including acetylsalicylic acid (aspirin) and celecoxib (Celebrex, Pfizer), are also directed against lipid-metabolizing enzymes. However, not all lipids are bad for us. Actually, some lipids promote health, such as omega-3 fatty acids and vitamins A, D, and E, and those benefits explain their exponential growth as food supplements and nutraceuticals.

New research in lipid biology suggests that, especially in the areas of drug discovery and disease diagnostics, we may have formerly adopted a myopic view of lipid metabolism. For years, biomedical research focused on analyzing only a handful of lipids. From the extrapolated results of those narrowly focused analyses, we sought to understand more than we could reasonably expect to know: the multifaceted mechanisms of action and the effects of drugs, the causes of complex diseases, and the intricate biological alterations associated with those diseases.


Figure 1: Representative structures for major lipid categories and examples of core structures in red.
As we move into a new era of lipid analysis, the potential to accurately and rapidly measure hundreds of individual molecular species provides the opportunity to use more complex lipid profiles for drug discovery and disease diagnostics. Because lipids are present in all living organisms, other areas of applications such as plant, microbial, and nutritional research also could benefit from improvements in lipid analysis and a better understanding of lipid metabolism.

Types of Lipids

Lipids constitute one of the largest classes of biological macromolecules. Together with nucleic acids, proteins, and carbohydrates, they are present in living organisms that span the spectrum of biological complexity: animals, plants, fungi, protists, bacteria, archaea, and viruses. Chemically, lipids are hydrophobic or amphipathic small molecules (<1500 Da) of biosynthetic origin, which can be counted on the order of tens of thousands. Lipids have enormously diverse chemical structures (Figure 1) and are classified into eight main categories (3):

  • fatty acyl
  • glycerolipids
  • glycerophospholipids
  • sphingolipids
  • sterol lipids
  • prenol lipids
  • saccharolipids
  • polyketides.

Each lipid heads its own subclassification hierarchy, according to the classification system proposed by the Lipid Metabolites and Pathways Strategy consortium (LIPID MAPS, La Jolla, California; http://www.lipidmaps.org/).

Several websites provide useful overviews of lipid structure and function, as well as analytical procedures for lipid analysis: Lipid Library (lipidlibrary.co.uk/), Lipid Bank (lipidbank.jp), and the Cyberlipid Center ( http://www.cyberlipid.org/).

Parallel to the development of new technologies is how our understanding of the biological role of lipids has changed with time. Lipids were known to serve as the structural backbone of cell membranes and as storage for metabolic energy. Recently, the biomedical community learned that lipids play pivotal roles in regulating a wide variety of cellular processes in all organisms. Within each cell exist thousands of types of lipids whose composition, or lipid profile, changes in response to chemical signals from the cell's environment. Studying lipid profiles can provide insight to certain health and disease processes.

Comprehensive analysis of a wide array of lipids in biological samples is a challenge primarily for analytical chemistry. These complex mixtures of lipids have a large variety of chemical structures and a large, dynamic range of concentrations. Consequently, interest in adapting novel technologies for lipids analysis continues undiminished.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters
Global E-newsletters subscribe here:




 

LCGC COLUMNISTS 2014

Sample Prep Perspectives | Ronald E. Majors: Ron Majors, established authority on new column technologies, keeps readers up-to-date with new sample preparation trends in all branches of chromatography and reviews developments.
LATEST: UV Detector Problems


Perspectives in Modern HPLC | Michael W. Dong: Michael W. Dong is a senior scientist in Small Molecule Drug Discovery at Genentech in South San Francisco, California. He is responsible for new technologies, automation, and supporting late-stage research projects in small molecule analytical chemistry and QC of small molecule pharmaceutical sciences. LATEST: Superficially Porous Particles: Perspectives, Practices, and Trends


MS — The Practical Art | Kate Yu: Kate Yu brings her expertise in the field of mass spectrometry and hyphenated techniques to the pages of LCGC. In this column she examines the mass spectrometric side of coupled liquid and gas-phase systems. Troubleshooting-style articles provide readers with invaluable advice for getting the most from their mass spectrometers. LATEST: Radical Mass Spectrometry as a New Frontier for Bioanalysis


LC Troubleshooting | John Dolan: LC Troubleshooting sets about making HPLC methods easier to master. By covering the basics of liquid chromatography separations and instrumentation, John Dolan is able to highlight common problems and provide remedies for them. LATEST: Problems with Large-Molecule Separations


More LCGC Chromatography-Related Columnists>>

LCGC North America Editorial Advisory Board>>

LCGC Europe Editorial Advisory Board>>

LCGC Editorial Team Contacts>>


Source: LCGC North America,
Click here