Topic overview

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Metabolism of xenobiotics occurs mainly in the liver’s endoplasmic reticulum and cytosol, with the broad aim of increasing polarity to support renal or biliary excretion. Phase I reactions—oxidation, reduction, and hydrolysis—can expose functional groups but may also generate reactive intermediates and reactive oxygen species. Phase II reactions conjugate compounds with groups such as glutathione, sulfate, or glucuronic acid; limited conjugation capacity can increase toxicity risk. The lesson’s examples show how CYP-mediated bioactivation contributes to carcinogen-related DNA damage and how NAPQI formation is involved in acetaminophen toxicity. It also considers oxidant-induced methemoglobinemia, CYP induction or inhibition, genetic variation, enterohepatic recycling, and the bioaccumulation of lipophilic compounds.