Topic overview

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Phase I reactions—oxidation, reduction, and hydrolysis—introduce or uncover polar groups. They occur largely through CYP450 enzymes in the smooth endoplasmic reticulum, with additional contributions from non-microsomal enzymes. CYP450 activity can vary because of genetic differences and exposure to enzyme inducers or inhibitors. In Phase II, enzymes attach endogenous groups to metabolites, generally increasing water solubility and supporting excretion; however, some conjugates remain active, and pathway limits can contribute to toxicity. Phase III transporters move conjugates across membranes for removal. Together, these phases provide a framework for understanding how xenobiotics are processed, while recognizing that Phase I may increase, reduce, or create activity and Phase II does not invariably end it.