Omeprazole is a proton pump inhibitor. The step at which it becomes an active sulfenamide is:
- A In the acidic secretory canaliculus of the parietal cell, where low pH converts omeprazole to the active tetracyclic sulfenamide ✓
- B In the blood, by plasma esterases activating the pro-drug
- C In hepatocytes during CYP2C19-mediated hydroxylation
- D In the gastric lumen, where HCl directly converts omeprazole to its active form
Explanation
Omeprazole is a prodrug (benzimidazole). When concentrated in the highly acidic secretory canaliculus (pH ~2) of the parietal cell, it undergoes acid-catalysed conversion to the active sulfenamide (tetracyclic form), which irreversibly covalently binds to the cysteine residues (Cys813, Cys892) of the H+/K+-ATPase (proton pump). This selective accumulation in the parietal canaliculus is why omeprazole is activated at the site of action without affecting other tissues. CYP2C19 metabolises omeprazole to its hepatic inactive hydroxyl metabolite, not to the active sulfenamide.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.