Xenobiotic metabolism system

The term "Detoxify" refers to the biological process of xenobiotic metabolism, a critical physiological system primarily centered in the liver that neutralizes and eliminates foreign chemicals (xenobiotics) and endogenous waste products. This system is organized into three distinct phases: Phase I involves modification (typically oxidation) by enzymes such as the Cytochrome P450 (CYP) family; Phase II involves conjugation of these intermediates to polar molecules via enzymes like Glutathione S-transferases (GST) and UDP-glucuronosyltransferases (UGT); and Phase III involves the active transport of these water-soluble products out of the cell for excretion via ABC transporters like P-glycoprotein. The system is regulated by master xenosensors, including the Pregnane X receptor (PXR) and the Constitutive Androstane receptor (CAR), which induce enzyme expression in response to toxicant exposure. While the process itself is not a single molecular target, its constituent enzymes and regulatory receptors are frequently targeted in pharmacology to manage drug-drug interactions, treat acute poisoning, or address chemoresistance in oncology.

Other names

Xenobiotic metabolismPhase I/II/III metabolismMetabolic detoxificationDrug metabolism systemBiotransformation system

Drugs interact with this system by serving as ligands for nuclear receptors (e.g., PXR, CAR, Nrf2) to induce the expression of metabolic enzymes and transporters, or by directly inhibiting specific enzymes (e.g., CYP3A4) to alter the clearance and therapeutic window of co-administered medications.