Mass spectrometry

I enjoyed reading Celia Henry Arnaud's article, "Mass Spec Tackles Proteins" about how "mass spectrometry shines in applications from proteomics to structural biology" (C&EN, Oct. 2, page 17). In particular, Arnaud points out some of the latest developments in the use of mass spectrometry to understand protein function, especially now that new techniques enable the study of intact proteins.

I'd like to point out another area where mass spectrometry has enabled biology to advance rapidly-namely, metabolomics. Metabolomics has evolved from an NMR-based research platform to one that now incorporates mass spectrometry and label-based techniques.

Metabolomics is the study of small endogenous molecules that reveal activity within biochemical pathways. The most recent form of mass-spec-based metabolomics, "tracer-based metabolomics" (sometimes referred to as SiDMAP in the scientific literature), uses ¹³C-labeled molecules that are incorporated into metabolic pathways of the cell. The mass spec is used to identify the metabolite as well as to measure the number and position of the ¹³C within the metabolite. By following which identified metabolites contain certain numbers of ¹³C, and by using various mass spec techniques to calculate the position of the ¹³C label within the molecular structure of the identified metabolite, tracer-based metabolomics is able to quantify the activity within identified biochemical pathways.

The mass spec analysis can be accomplished in tissue samples, body-fluid samples, or breath samples and is perfectly safe in humans. Thus, tracer-based metabolomics is making great strides in revealing the biochemical changes underlying human disease and in the treatment of these diseases with new drugs or biologics.

Greg Maguire
San Diego