Metabolites play an important part in living cells by connecting many different active pathways as biological intermediates of biochemical reactions, Metabolite levels render a unique chemical fingerprint for a physiological cellular state of a cell, thereby defining the cell phenotype which can be assessed by the metabolite profile. Due to the large number of analytes, a customized quenching and extraction protocol, as well as a highly sophisticated metabolite detection and data assessment method are necessary.
When addressing complex systems such as the human body, blood plasma and serum are the samples of choice for metabolite profiling studies. Since profound physiological influences caused by cerebral, cardiac or hepatic effects are directly reflected in the blood metabolome, it is possible to detect these changes via the investigation of blood metabolites. Specific sample extraction protocols and sensitive analysis methods allow the detection of naturally occurring chemical substances in the body, as well as xeno-metabolites, with the possibility to identify biomarkers for a wide range of diseases and metabolic states.
In general metabolomics analyzes all metabolites present in a sample, while targeted metabolomics tries to address a (pre-) selected number of metabolites, ranging from half a dozen to hundreds of metabolites. To achieve this goal, the optimal analysis method can be chosen from different approaches with the most common being GC/MS, (U)HPLC/MS or CE/MS. Depending on the compounds of interest, each technique has its advantages and disadvantages. Because of the progress in mass spectrometry-based metabolomics, a wide variety of chromatographic metabolite separation, followed by various ionization and analysis options via mass spectrometers is available.
Metabolomics is the latest “omics”-branch which has a focus on the identification and quantification of small molecules (<1500 Da). Metabolites provide the most comprehensive measure of dynamic processes for different phenotypes and medical conditions as they fall downstream of genetic, transcriptomic, proteomic and environmental variation.
Therefore, metabolomics is a perfect starting point to generate hypotheses for metabolic influences on the phenotype and possible biomarkers for medical conditions. Biological systems can be perturbed by diseases, gene mutations, environmental factors or, for example, by changes in the microbiome. After the initial perturbation, strong compensatory effects in the metabolic system can keep the organism in an apparently healthy state for a long time. Metabolomics is able to reveal affected metabolic pathways in perturbed biological systems and guide necessary extensive research activities.