Biochemistry · Enzyme
H⁺/K⁺-ATPase (gastric proton pump) !
The gastric proton pump spends ATP to swap H⁺ for K⁺ and makes stomach acid. Proton pump inhibitors block it.
Updated 2026-11-01
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Key facts
- Each ATP pumps H⁺ out into the gastric lumen in exchange for K⁺ coming in.
- It builds a gradient of about a million-fold and can bring gastric juice down to pH 1.
- A P-type ATPase like the sodium pump: a brief phosphorylation drives the switch between inward-facing (E1) and outward-facing (E2) states.
- Found in parietal cells, in the apical (canalicular) membrane; it is the final step of acid secretion.
Structure
- Catalytic α chain (ATP4A, 1035 amino acids) paired with a β subunit (ATP4B).
- Structure 5YLU is the pig gastric pump with vonoprazan, a potassium-competitive acid blocker, in the K⁺ path.
Regulation
- The β subunit (ATP4B) holds the pump in the E2 state and prevents the reverse reaction.
Inhibitors and toxins
- Proton pump inhibitors (omeprazole): substituted benzimidazoles whose binding to the pump outlasts the drug in the blood.
- Potassium-competitive acid blockers (vonoprazan): compete with K⁺.
Clinical notes
- Blocking the last step lowers acid whatever the stimulus: used in GERD, ulcers, H. pylori treatment (with antibiotics) and Zollinger–Ellison syndrome.
- Long-term use has been linked to low magnesium and to vitamin B12 malabsorption.
- Omeprazole is broken down by acid, so it is given in a coated form.
Drugs that act here
Related conditions
- Gastro-oesophageal reflux disease (GERD)
- Peptic ulcer disease
- Helicobacter pylori gastritis
- Upper gastrointestinal bleeding
Related
Test yourself
Think of the answer, then tap the question to see it.
Which ions does the gastric proton pump exchange?
It pumps H⁺ into the gastric lumen and brings K⁺ into the parietal cell, using ATP.
Why do proton pump inhibitors reduce acid whatever the stimulus?
They act on the final step of acid secretion, shared by every stimulus.
Which long-term effects of PPIs relate to absorption and minerals?
Low magnesium and poor vitamin B12 absorption.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: ATP4A: Potassium-transporting ATPase alpha chain 1 (human) (UniProt, 2026); 5YLU: Crystal structure of the gastric proton pump complexed with vonoprazan (RCSB Protein Data Bank, 2026); OMEPRAZOLE capsule, delayed release (DailyMed, US National Library of Medicine, 2026); Omeprazole: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.