Author: Simone Maimon
Editors: Ethan Tai, Jonathan Chen
Artist: Emily Tai
Scientists uncover the secrets of the natural world around them using three methods of biological analysis: genomics, the study of the genome; proteomics, the study of proteins; and metabolomics, the analysis of metabolites, or small molecules. Metabolomics has only recently become widely researched, as the thousands of compounds in a sample made it difficult to effectively study them without modern technology. The field has already revealed numerous molecules that can reveal a patient’s condition. Scientists use two methods of metabolomics analysis: targeted and untargeted. The former focuses on a few molecules known to be in the sample, which can be useful for comparing specific quantities of one metabolite across multiple samples. The latter detects a broader spectrum of molecules, which is useful for creating a metabolomic profile, or a collection of the metabolites in a sample. This article discusses the technology that has allowed metabolomics to become a tool for research and medicine.
Though the idea behind metabolomics is simple, it wasn’t widely studied until recently. Without modern methods of metabolomic analysis, it was nearly impossible to figure out the specific molecules in a solution. Only over the past two decades have scientists started to focus on compound identification and quantification in organisms, even though mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy—the two main methods of metabolomic analysis—were discovered in the early 1900s. In mass spectrometry, the machine first ionizes and then accelerates the molecules in a solution. The compounds pick up different speeds based on their mass-to-charge ratio, thereby allowing the machine to detect the mass of the compound extremely accurately. From this data, scientists can try to identify certain compounds present in the material—which can be tricky if multiple isotopes have extremely similar masses and characteristics. While mass spectrometry is good for analyzing compounds extracted in fluids, NMR spectroscopy can be used to analyze compounds in semi-solid and solid samples, including intact tissues and organs. NMR uses strong magnetic fields combined with radiofrequency pulses to ultimately determine the positions of nuclei in compounds and their structure in the sample. However, NMR spectrometry is often ten to one hundred times less sensitive than mass spectrometry. Nevertheless, NMR is more useful for quantifying compounds, as mass spectrometry often needs to be coupled with liquid or gas chromatography to determine compound concentration.
Although it is still being developed, scientists have been looking into metabolomic analysis as a marker for disease in patients. For example, metabolomics has been useful in understanding the effects and causes of obesity on the human body. Doctors have been able to predict the BMI of subjects with some accuracy using metabolomic analysis—revealing obesity is correlated with an altered metabolism. In obese patients, they discovered there tends to be an increased amount of glucose and branched-chain amino acids. With further research, scientists may be able to figure out how metabolic disorders like type II diabetes are caused by adiposity. Metabolite analysis can reveal more than just metabolic disorders. After enough research has been done on a disease, if there are molecules in abnormal quantities that are correlated with the disease, scientists can put together a ‘metabolic profile’ that can be used as a standard to compare to actual patient samples. Eventually, metabolomics may be able to reveal otherwise invisible illnesses such as small-cell lung cancer, gout, sepsis, and Alzheimer's disease.
Metabolomics is also used with genomic analysis to better understand metabolic pathways. Scientists have associated numerous genetic sequences in our DNA that are associated with our metabolism; they discovered over 400 independent genomic regions that affect 233 metabolic markers circulating in the body. In future research, scientists aim to use metabolomics to better understand the metabolic pathways in our body, which can lead to cures for metabolic disorders.
Metabolomics has become increasingly popular in the 21st century because of technological advances like NMR spectroscopy and mass spectrometry. As scientists develop clinical uses of metabolomics to diagnose diseases, they are also researching other uses of metabolomics. Rather than analyzing human samples, metabolite analysis has also been used for plant and animal matter as well. Some plants produce medicinal compounds; metabolomics can be used on these plants to determine which molecules are responsible for their medicinal properties. Metabolomics is useful for studying any type of compound in an organism, whether it indicates poor health or reveals potential medicinal chemicals.
Citations:
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U.S. National Library of Medicine, 27 June 2019,
D’Alessandro, Angelo, et al. “Clinical Metabolomics: The Next Stage of Clinical
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Medicine, May 2012, pmc.ncbi.nlm.nih.gov/articles/PMC3418628/.
Dalamaga, Maria. “Clinical Metabolomics: Useful Insights, Perspectives and Challenges.”
Metabolism Open, Elsevier, 31 May 2024,
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