metabolism
Definition
Metabolism refers to the biochemical transformation of drugs, xenobiotics, and endogenous compounds within living organisms, primarily occurring in the liver through Phase I (functionalization) and Phase II (conjugation) reactions. This process is critical in pharmacology as it determines drug bioavailability, duration of action, and elimination. Cytochrome P450 enzymes (CYPs) are the primary catalysts for Phase I metabolism, while transferases mediate Phase II reactions. Metabolic pathways can produce active, inactive, or toxic metabolites, directly impacting therapeutic efficacy and safety. Understanding metabolism is essential for predicting drug-drug interactions, individual variability in drug response, and designing prodrugs that require metabolic activation to achieve therapeutic effects.
Visualize metabolism in Nodes Bio
Researchers can visualize metabolic pathways as networks connecting parent compounds to metabolites through enzymatic reactions. Nodes Bio enables mapping of drug-enzyme-metabolite relationships, identifying key metabolic nodes like CYP450 isoforms, and analyzing how genetic polymorphisms or co-administered drugs affect metabolic flux. Users can overlay expression data to predict tissue-specific metabolism or trace metabolite formation cascades to identify potential toxic intermediates.
Visualization Ideas:
- Drug-enzyme-metabolite cascade networks showing Phase I and Phase II transformation pathways
- CYP450 substrate-inhibitor-inducer interaction networks for predicting drug-drug interactions
- Tissue-specific metabolic networks integrating enzyme expression data with compound biotransformation routes
Example Use Case
A pharmaceutical team investigating why their experimental antidepressant shows variable efficacy across patient populations uses network analysis to map its metabolic pathway. They discover the drug undergoes extensive CYP2D6-mediated metabolism to form an active metabolite. By visualizing the network of metabolizing enzymes, genetic variants, and metabolite activity profiles, they identify that CYP2D6 poor metabolizers receive insufficient active drug, explaining the therapeutic failures. This insight guides development of a companion diagnostic test for patient stratification.