Your Guide to Metabolomics

Chapter 1—Metabolomics, Metabolites, and the Metabolome

It’s no secret—multi-omics research is quickly becoming the new standard in human disease research.
scientists guide to metabolomics

What is Metabolism?

Metabolism is the set of life-sustaining chemical reactions in organisms. The main purposes of metabolism are to: convert food or fuel to energy so that cellular processes can run; convert food to building blocks for proteins, lipids, nucleic acids and carbohydrates; and to eliminate metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow, reproduce, maintain their structures, and respond to their environment.

What is Metabolomics?

Metabolomics is the identification of small molecules known as metabolites.1 Metabolomics is a powerful companion to other commonly used omics techniques: genomics, transcriptomics, and proteomics. While these techniques provide information about genetic and functional potential, metabolomics goes a layer deeper by providing phenotypic information. Our genomes, transcriptomes, proteomes, and metabolomes don’t exist in a vacuum—they impact and are impacted by one another as well as by the outside environment (Figure 1).
figure1
Figure 1. The complex interrelationship between genes, environment, and functional capacity.

The genome, studied via genomics, provides all of the information necessary for creating a functional organism. The transcriptome, studied via transcriptomics, reveals which genes are actually being turned into transcripts as well as which non-coding RNAs are present and can elucidate effects on the genome or even on the proteome and metabolome. The proteome, studied via proteomics, is the collection of proteins that have actually been translated from RNA transcripts. Finally, the metabolome, studied via metabolomics, includes all small molecules included that are present in an organism under a certain set of conditions. While each of these molecules can influence any of the others, environmental factors, such as therapeutic treatments, can also critically impact gene expression, regulation, protein folding, and metabolic function.

The information gathered from genomics, transcriptomics, proteomics, and metabolomics, when combined (called multi-omics) provides a complete puzzle explaining the intricate regulatory and functional mechanisms behind living organisms. Think of it this way: other omics techniques—genomics, transcriptomics, and proteomics—can identify a tree as an apple tree, and even which kind of apple the tree produces. But metabolomics will tell you about the flavor profile of the apple, which antioxidants are present and how much, and how specific weather patterns have influenced those antioxidants. Such information can be useful for farmers to decide which plants to breed in the future and which might be the best candidates for commercialization. In the context of human health, metabolomics can help elucidate the molecular mechanisms behind the development of cancer (or any other disease), and why certain people respond to specific treatments but not others.2

What is a Metabolite?

Metabolites are small molecules less than 1.5 kDa in size.3 The end products of metabolism, metabolites have a wide range of functions, including cell growth support, defense and inhibition, and stimulation. They include amino acids, alcohols, vitamins, polyols, organic acids, and many other types of molecules, and are often the building blocks for larger compounds.2 Identifying metabolites and how they interact with one another—and how those interactions change under certain conditions—can aid in the discovery and understanding of how organisms work, why diseases develop (or not), why treatments are successful or not, and so much more.2

What is the Metabolome?

While the genome represents the entirety of genetic information encoded in DNA and the transcriptome all RNA transcripts, for example, the metabolome is the collection of all metabolites present in an organism. Metabolomes are incredibly fluid and can change drastically with differences in the outside environment, such as nutrient availability, medications, etc. Importantly, the metabolome doesn’t just include metabolites produced natively by an organism, but also metabolites produced by the microbiome residing in and on that organism. Microbial metabolites, for example, can have a significant impact on the metabolism of therapeutics inside the host and can impact whether or not medications such as chemotherapy are effective.2

What is a Genotype?

Genotype refers to an individual’s genes and DNA that determine its phenotype.

In other words, it is the “blueprint” for an organism’s physical characteristics. The genotype is determined by the genes that are inherited from the organism’s parents. The genotype is always present and will ultimately determine the phenotype. Therefore, it is important to know the genotype of an organism in order to predict its phenotype.

What is a Phenotype?

Phenotype is the set of characteristics of an organism that are determined by a combination of genetics and the environment.

The term phenotype includes all physical and functional characteristics of an organism, from its morphology to its behavior. Many phenotypic traits are determined by a single gene, but most are the result of the interplay of multiple genes and the environment. The environment can influence phenotypic traits in many ways, including through nutrition, temperature, toxins, and stress. As a result, phenotype is often used as a general term for the overall appearance and function of an organism, rather than referring to a specific trait.

References

1. Liu X, Locasale JW. Metabolomics: A Primer. Trends Biochem Sci. 2017;42(4):274-284. doi:10.1016/j.tibs.2017.01.004

2. Ashrafian H, Sounderajah V, Glen R, et al. Metabolomics: The Stethoscope for the Twenty-First Century. Med Princ Pract. 2021;30(4):301-310. doi:10.1159/000513545

3. Wishart DS, Tzur D, Knox C, et al. HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007;35(Database issue):D521-D526. doi:10.1093/nar/gkl923

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