Phase I drug-metabolizing enzyme

Phase I drug-metabolizing enzymes are a diverse group of proteins responsible for the initial biotransformation of xenobiotics, including most clinical drugs, and endogenous compounds. These enzymes primarily function by introducing or unmasking polar functional groups through oxidation, reduction, and hydrolysis reactions, a process often referred to as functionalization (NCBI, PMC3075480). The most prominent members are the Cytochrome P450 (CYP) superfamily, which handles approximately 75% of drug metabolism, but the class also includes flavin-containing monooxygenases (FMOs), alcohol/aldehyde dehydrogenases, and esterases (StatPearls, NBK542187). By altering the chemical structure of a molecule, these enzymes can terminate the action of a drug, activate a prodrug into its active form, or occasionally generate reactive intermediates that lead to toxicity. Genetic polymorphisms in these enzymes are a major source of inter-individual variability in drug response, making them a focal point for pharmacogenomics and personalized medicine (PubMed, 25124377). Understanding their inhibition and induction is critical for avoiding adverse drug-drug interactions in clinical practice.

Other names

Phase I enzymesFunctionalization enzymesBiotransformation enzymesNon-conjugative enzymes

Phase I enzymes catalyze the introduction or unmasking of functional groups (e.g., -OH, -NH2, -SH) through oxidation, reduction, or hydrolysis, typically increasing the polarity of the substrate to facilitate excretion or subsequent Phase II conjugation (StatPearls, NBK542187).