xenobiotic detoxification by transmembrane export across the plasma membrane

Definition

Target type: biologicalprocess

A process that reduces or removes the toxicity of a xenobiotic by exporting it outside the cell. [PMID:28355133]

Xenobiotic detoxification via transmembrane export across the plasma membrane is a crucial process in protecting organisms from harmful foreign compounds. This complex mechanism involves a series of steps, each relying on specialized proteins and enzymatic activities. Here's a detailed breakdown:

1. **Xenobiotic Uptake:** The journey begins with the entry of xenobiotics into the cell, often through passive diffusion across the cell membrane. This process is influenced by factors like the xenobiotic's lipid solubility and size.

2. **Metabolic Transformation:** Once inside, xenobiotics are often subjected to enzymatic modification. This transformation is critical in converting the xenobiotic into a more water-soluble form, facilitating its excretion. Two primary phases are involved:

* **Phase I:** This phase primarily involves oxidation, reduction, or hydrolysis reactions catalyzed by enzymes like cytochrome P450 monooxygenases (CYPs). These reactions introduce functional groups (e.g., hydroxyl, carboxyl) that increase the compound's polarity.

* **Phase II:** Here, conjugating enzymes attach polar groups (e.g., glutathione, glucuronic acid) to the xenobiotic. This conjugation further enhances water solubility, marking the compound for removal.

3. **Transmembrane Export:** The modified xenobiotics, now more polar and water-soluble, are ready for export. This step is accomplished by transmembrane efflux transporters, which are specialized proteins embedded within the plasma membrane.

4. **Efflux Transporter Mechanisms:** These transporters utilize various mechanisms for extrusion:

* **ATP-Binding Cassette (ABC) Transporters:** This family of transporters, including P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), are driven by ATP hydrolysis, actively expelling xenobiotics out of the cell.

* **Secondary Active Transporters:** These transporters leverage the electrochemical gradient of another molecule (e.g., protons) to move the xenobiotic against its concentration gradient.

5. **Excretion:** The extruded xenobiotics are then removed from the body through various routes, including urine, bile, and feces. This final step ensures the complete elimination of the toxic compounds.

In summary, xenobiotic detoxification via transmembrane export involves a multi-step process encompassing uptake, metabolic transformation, and active transport across the plasma membrane. This coordinated action of enzymes and transporters safeguards the organism from the harmful effects of foreign compounds.'
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Proteins (7)

Compounds (329)