Substrate
Definition:
In the context of metabolism, substrates are drugs that bind to an enzyme’s active site. These active sites are usually very specific and will only bind to select ligands. While in the active site, the drug can then be turned into metabolites. Depending on the transformation, multiple enzymes can be used on the same drug to create different metabolites. Typically, these drugs undergo metabolism to be converted from an active form to an inactive form for clearance. Alternatively, the opposite is also true, and they need to be converted to an active form.
Relevance:
Drug metabolism is extremely important and understanding how drug substrates interact with enzymes to create the resultant metabolites allows for researchers to understand what the drug is most useful for treating.
Enzymes can also only work on substrates in a specific environment, with factors including pH and temperature. This ensures substrate specificity, so knowing the characteristics of substrates allows for better drug design.
Example:
Warfarin is a drug that acts as a substrate for CYP enzymes, specifically CYP3A4. CYP enzymes primarily work by adding an oxygen atom to the substrate.
Linked terms: Drug Mechanisms, Inducer, Enzyme, Drug Clearance, Metabolism, Absorption, affinity, metabolite, biotransformation, Active site, Enzyme-substrate complex, Allosteric site, Competitive inhibitor, Non-competitive inhibitor
Resources:
Angel, R., & Sorbara, J. O. B. (2014). Why is it important to understand substrates if we are to optimize exogenous enzyme efficacy? Poultry Science, 93(9), 2375–2379. https://doi.org/10.3382/ps.2013-03869
Deodhar, M., Al Rihani, S. B., Arwood, M. J., Darakjian, L., Dow, P., Turgeon, J., & Michaud, V. (2020). Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice. Pharmaceutics, 12(9), 846. https://doi.org/10.3390/pharmaceutics12090846
Forgione, J. V., & Randall, D. (Eds.). (n.d.). Cytochrome P450 Drug Metabolism. Dynamed. https://www.dynamed.com/drug-review/cytochrome-p450-drug-metabolism#GUID-13B09D14-50BB-4283-9B41-7F0A9456080D
Gilani, B., & Cassagnol, M. (2024). Biochemistry, Cytochrome P450. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK557698/
Lewis, T., & Stone, W. L. (2024). Biochemistry, Proteins Enzymes. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK554481/
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