Thematic Minireview Series on Biological Applications of Mass Spectrometry

Abstract

Mass spectrometry is a powerful technique with many applications in biology as well as chemistry and physics. The increases in sensitivity and resolution of the instruments, coupled with improvements in the analysis of data, have opened new dimensions in analyses of complex biological systems. Examples presented here include drug metabolism, lipid analysis, metabolomics, quantitative proteomics, direct analysis of intact proteins, and imaging of both small molecules and proteins in tissues.

Introduction

Mass spectrometry is not a new analytical method, going back more than 100 years to work on mass/charge ratio determination by W. Wien, J. J. Thomson, and other physicists (1). Mass spectrometers perform one simple measurement: the analysis of mass. Early work in the field led to the discovery of isotopes and, by the 1930s, the association with chemical structures. Mass spectrometry became essential in the characterization of natural products and synthetic chemicals, leading to biological applications. Some major advances included the use of isotopic labeling methods, direct coupling to gas and then liquid chromatography, and introduction of softer ionization methods allowing for the direct analysis of macromolecules (2).

The first of the six minireviews in this series, by Mingshe Zhu, Haiying Zhang, and W. Griffith Humphreys, deals with modern applications of high-resolution mass spectrometry to the metabolism of drugs. In particular, so-called “mass defect” screening makes use of the small non-integral differences in molecular masses to facilitate the analysis of metabolites of drugs in complex biological systems. These methods can, of course, be applied to studies of the metabolism of other small molecules.

The second minireview, by Robert C. Murphy and Simon J. Gaskell, addresses lipids and applications of mass spectrometry, including the topics of lipidomics, modern approaches to lipid quantitation and double bond positional analysis, ion mobility analysis, and imaging in tissues.

The third minireview, by Zhentian Lei, David V. Huhman, and Lloyd W. Sumner, deals with metabolomics and the use of mass spectrometry to study complex aspects of metabolism. This field is growing in applications in plant science, human disease, and many other areas and is the subject of many symposia, etc. Instrumental and experimental design issues are discussed.

The fourth minireview, by Fang Xie, Tao Liu, Wei-Jun Qian, Vladislav A. Petyuk, and Richard D. Smith, focuses on proteomics, particularly quantitative analysis of proteins in these studies. This is a more challenging problem than in the case of mRNA profiling, but a number of major advances have been made with isotopic labels.

The fifth minireview, by Jeremiah D. Tipton, John C. Tran, Adam D. Catherman, Dorothy R. Ahlf, Kenneth R. Durbin, and Neil L. Kelleher, also deals with aspects of proteomics but with a different objective: the analysis of intact proteins by mass spectrometry (a feat few imaged 40 years ago). There are a number of reasons to analyze intact proteins rather than peptides, as explained here.

The final minireview in this series, by Erin H. Seeley, Kristina Schwamborn, and Richard M. Caprioli, deals with the use of mass spectrometry in imaging both small molecules and macromolecules in intact tissues. The concept of using mass as an imaging parameter leads to potentially exquisite selectivity for maps of molecules in cells and avoids the use of labeled probes and specificity issues.

These are not the only uses of mass spectrometry in biology, but they touch on some of the most important ones. Other topics for future minireviews may include analysis of nucleic acids by mass spectrometry, use of carbon dating mass spectrometry approaches in analysis of steroids and doping, metabolism analysis with accelerator mass spectrometry, and other analyses of metabolomic data. An effort has been made to make all of these minireviews readable by non-specialists. I hope that these minireviews will enhance each reader's research in some way.