Metabolomics Research

Illustrating a cell surrounded by structures of metabolites represented as a galaxy.

Metabolomics is the comprehensive study of metabolites, or the small molecule substrates, intermediates and products of metabolism, within cells, biofluids, tissues, or organisms. These unique chemical fingerprints are left behind by cellular processes. Metabolomics research provides a biochemical synopsis of a biological system and the physiological impact of disease, nutrition, therapy, or genetic modifications on an organism. Common applications for studying human, microbial or plant metabolomics include:

  • pharmaceutical research to help characterize and identify novel biomarkers of disease and assess toxicity for personalized medicine
  • functional genomics integration, or the study of the interaction of the genome, transcriptome, proteome and metabolome to predict gene function
  • microbial mining and strain optimization
  • plant metabolomics for agriculture biotechnology
  • environmental research to test the effects of pollutants in aquatic or terrestrial ecosystems and optimize the production of biofuels
  • nutritional research to assess nutrition levels and perform food safety testing

The interaction of metabolites within a biological system is referred to as the metabolome. The metabolome is the complete set of metabolites in an organism or biological sample. Metabolites are compounds with low molecular weight, generally less than 1.5 KDa, which are the intermediates or products of biosynthesis/catabolism pathways. Examples include amino acids, nucleotides, carbohydrates, and lipids, which are often studied separately in lipidomics research. Primary metabolites are endogenous and directly involved in normal growth, development, and reproduction. Secondary metabolites are exogenous and not involved in these processes but have important ecological functions.

Metabolomic pathways are investigated utilizing metabolites, enzymes, separation tools, and metabolite analysis and labeling. Two of the most common metabolic profiling techniques are targeted and untargeted metabolomic analyses. Targeted metabolomic analysis is the quantification of specific known metabolites in a sample, usually within a defined pathway or related group of compounds. Untargeted metabolomic analysis provides the global metabolic profile of a sample for both known and unknown metabolites with the intention of identifying novel metabolites. Metabolic fingerprinting is a rapid, global analysis of metabolites in a sample without the intention of specifically identify each metabolite.

A metabolomics workflow involves an integrated approach of sample preparation, standardization and calibration, separation methods, detection of metabolites, and data analysis. Sample types include plasma, urine, saliva, tissue, and cells. Sample preparation and separation methods are necessary to simplify complex mixtures as it is difficult to simultaneously analyze a broad range of metabolites with various physiochemical properties. Common separation methods utilized are gas chromatography (GC), high performance liquid chromatography (HPLC), or capillary electrophoresis (CE). These separation methods are commonly paired with mass spectrometry as a detection method, GC-MS or LC-MS. Mass spectrometry (MS), nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy, and Raman spectroscopy are analytical techniques commonly used in metabolite detection. Metabolomics data analysis requires sophisticated tools and software for stringent compound identification and quantification, and accurate data interpretation.

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