Proton pump inhibitors (PPIs) irreversibly block gastric acid secretion. Their activation requires which specific condition?
- A Alkaline pH in the cytoplasm of gastric parietal cells
- B Phosphorylation by cAMP-dependent protein kinase A before binding the proton pump
- C Acid environment (pH < 4) in the secretory canaliculus to convert the prodrug to the active sulphenamide ✓
- D Conjugation with glutathione in the liver to the active thiol form
Explanation
PPIs (omeprazole, lansoprazole etc.) are prodrugs that are weak bases. They accumulate in the highly acidic secretory canaliculi of active parietal cells (pH 1–2), where they are protonated and undergo acid-catalysed conversion to the active sulphenamide (tetracyclic cationic form). This reactive metabolite covalently binds cysteine residues (Cys813 and Cys892) of the H+/K+-ATPase alpha subunit, permanently inactivating it. This selectivity for the acid environment explains why PPIs are pro-drugs and why they should be taken 30 minutes before meals (when parietal cells are most actively pumping).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.