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Metabolomics

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Metabolomics is the scientific study of chemical processes involving metabolites. These metabolites are small molecules that act as substrates, intermediates, and products of cell metabolism. The complete set of these molecules in a cell, tissue, or organism is called the metabolome. While other sciences look at the blueprints of life, metabolomics looks at the actual results.

To understand how this works, we must look at the flow of biological information. Genomics studies DNA to see what could happen in a cell. Transcriptomics looks at messenger RNA to see what appears to be happening. Proteomics examines proteins to see what makes processes happen. Finally, metabolomics shows what has happened and what is currently happening. It provides a direct functional readout of the physiological state of an organism. This makes it an instantaneous snapshot of how a cell is actually working.

Metabolites function within a complex, interconnected network of chemical reactions. This network is often described as a hypercycle. In a hypercycle, the output of one enzymatic reaction becomes the input for another. This creates a continuous loop of chemical activity. Scientists often study these molecules by collecting bio-specimens. Common samples include plasma, serum, urine, saliva, feces, muscle, sweat, and even exhaled breath. Because these samples are in dynamic equilibrium with the body, they can describe the host as a whole.

There are different ways to categorize these molecules depending on the organism. In plant-based studies, scientists distinguish between primary and secondary metabolites. Primary metabolites are directly involved in growth, development, and reproduction. Secondary metabolites are not essential for growth but serve important ecological functions, such as pigments or antibiotics. In human studies, metabolites are often described as endogenous or exogenous. Endogenous metabolites are produced by the host organism itself. Exogenous substances, such as drugs, are called xenometabolites.

The history of this field began in the late 1940s with Roger Williams. He suggested that individuals might have a unique metabolic profile in their biological fluids. He used paper chromatography to find patterns in urine and saliva. In 1971, the term "metabolic profile" was officially introduced by Horning and his team. They used gas chromatography-mass spectrometry, or GC-MS, to measure compounds in human tissue and urine. Other researchers, including Linus Pauling and Arthur B. Robinson, helped develop GC-MS methods throughout the 1970s.

Key stages of a metabolomics study
Key stages of a metabolomics study

Another vital tool is NMR spectroscopy, which was discovered in the 1940s. In 1974, Seeley and colleagues used NMR to detect metabolites in unmodified muscle samples. They discovered that 90% of cellular ATP is complexed with magnesium. Later, Jeremy K. Nicholson pioneered the use of pattern recognition with NMR data. In the 1990s, Gary Siuzdak and his colleagues used liquid chromatography mass spectrometry to study sleep-deprived animals. They identified a molecule called oleamide, which was later shown to have sleep-inducing properties.

Today, massive databases help scientists organize this complex information. The METLIN database was developed in 2005 at the Scripps Research Institute. As of December 2023, METLIN contains data on over 960,000 molecular standards. Another major effort is the Human Metabolome Project, led by David S. Wishart. In January 2007, they completed the first draft of the human metabolome. This draft included 2,500 metabolites, 1,200 drugs, and 3,500 food components.

Human metabolome project
Human metabolome project

The Human Metabolome Database (HMDB) is one of the most extensive public resources available. It contains 220,945 metabolite entries, including both lipid-soluble and water-soluble types. The database also links to 8,610 protein sequences, such as enzymes and transporters. Each entry can contain up to 130 data fields. This helps researchers in clinical chemistry and biomarker discovery. By integrating metabolomics with other "-omics" fields, scientists hope to achieve a complete understanding of cellular biology.

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File:The central dogma of biology showing the flow of information from DNA to the phenotype. Associated with each stage is the corresponding systems biology tool from genomics to genomics to metabolomics.png
The central dogma of biology showing the...
File:Human_metabolome_project.png
Human_metabolome_project.png
File:Key_stages_of_a_metabolomics_study.png
Key_stages_of_a_metabolomics_study.png
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