Phase I drug-metabolising enzyme

Phase I drug-metabolising enzymes are a large family of enzymes predominantly located in the endoplasmic reticulum of liver cells, although they are present in many tissues. They primarily function to introduce or expose functional groups (such as hydroxyl, amino, or carboxyl) to drugs and xenobiotics, increasing their polarity and making them more amenable to subsequent conjugation (phase II metabolism) and excretion. The most important subclass is the cytochrome P450 monooxygenases, which catalyze oxidation reactions, but phase I metabolism also includes reduction and hydrolysis. The activity of phase I enzymes determines the pharmacokinetics and efficacy of many medications, and can generate active metabolites (beneficial for prodrugs) or toxic intermediates (potentially harmful). Genetic, disease, and drug-induced variations in phase I enzyme activity have major clinical impact, including altered drug efficacy, adverse drug reactions, and drug-drug interactions. The term “Phase I drug-metabolising enzyme” is generic and should ideally be replaced by the specific enzyme isoform(s) involved.

Other names

Phase I enzymeDrug-metabolizing enzyme (DME)MonooxygenaseOxidative enzymeReductive enzymeHydrolytic enzyme

Oxidation (mainly via cytochrome P450 monooxygenases); Reduction; Hydrolysis; Induction or inhibition of enzyme activity by drugs or endogenous compounds