What are Metabolites?

By Dr. Tomislav Meštrović, MD, Ph.D.

An understanding of metabolism is pivotal to comprehending the phenotypic behavior of all living organisms (including humans) where metabolism is integral to health and proper functioning. Metabolites are the intermediate products of metabolic reactions catalyzed by various enzymes that naturally occur within cells. This term is usually used to describe small molecules, although broader application is often practiced.

Primary metabolites are synthesized by the cell because they are indispensable for their growth. Significant representatives are amino acids, alcohols, vitamins (B2 and B12), polyols, organic acids, as well as nucleotides (e.g. inosine-5'-monophosphate and guanosine-5'-monophosphate).

Secondary metabolites are compounds produced by an organism that are not required for primary metabolic processes, although they can have important ecologic and other functions. They include drugs, fragrances, flavor, dye, pigments, pesticides and food additives with applications in agriculture, industry and pharmaceuticals.

Human metabolites

Arachidonic acid is a metabolite of prostaglandin and both molecules contain similar functional groups, have similar physical properties and demonstrate nearly identical formulas. In addition, both compounds are linked by a defined series of enzyme-catalyzed reactions with a logical progression of chemical change. Inosine-5'-monophosphate is a metabolite that arises by condensing two or more intermediates (namely phosphoribosyl-pyrophosphate and glutamine) with a one way directionality based on the principles of free energy exchange.

Steroid hormones are derived from cholesterol via minimal changes to the superstructure of the cholesterol ring, which gives them biochemical functionality different from the original molecule. Catecholamines (such as norepinephrine or dopamine) arise from the amino acid tyrosine in an irreversible pathway. In addition, biochemical laws necessitate all precursors of catecholamine to go through a tyrosine intermediate.

Precise definition of small molecules is hindered by the fact that they rapidly lose any resemblance to the parent structure. Metabolite can also represent a building block of a larger structure or a degraded product destined for excretion.

Metabolomics is the study of an organism’s metabolome, which is the collection of metabolites found in particular organism. It is complementary to gene expression and proteomic studies. The Human Metabolome Database (HMDB) represents a freely accessible electronic database holding detailed information about small molecule metabolites found in the human body.

Microbial metabolites

Microbial metabolites represent an amazingly diverse array of chemistry. The chemical diversity found in the thousands of metabolites made by microorganisms remains an unmatched resource for the discovery of novel microbial compounds that may be useful in human applications.

The distinction between the primary and secondary metabolites of microorganisms is not straightforward. They often produce not just one member of a metabolite class, but a complex mixture of analogues (i.e. metabolites with closely related chemical structures).

Production and secretion of microbial secondary metabolites is thought to give the producers a competitive advantage in their native environments through suppressed growth of neighboring species, more efficient foraging or some other mechanisms.

Within the field of industrial microbiology, alcohol is considered one of the most common primary metabolites employed for large-scale production. This metabolite is used for processes involving fermentation which results in end-products like beer and wine.

Citric acid, produced by Aspergillus niger, is one of the most widely used ingredients in food production, but is also used in pharmaceutical and cosmetic industries. Antimicrobial metabolites like bafilomycin, geldanamycin, herbimycin, tautomycin and leptomycin have all established important roles as bioprobes in cell biology.

Examples of secondary metabolites with importance for human health include atropine and antibiotics such as erythromycin and bacitracin. Atropine is a secondary metabolite derived from various plants with important use in the clinic.