Chapter 1—Metabolomics, Metabolites, and the Metabolome

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 eliminate metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow, reproduce, maintain their structures, and respond to their environment.

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.

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

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.

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.

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