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[Biochemistry](https://durgical.com/en/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.

**Also called**
Proton pump

**EC number**
[7.2.2.19](https://www.enzyme-database.org/query.php?ec=7.2.2.19)

**Genes**
ATP4A

**Structure (PDB)**
[5YLU](https://www.rcsb.org/structure/5YLU)

## 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

- [Pantoprazole](https://durgical.com/en/pharmacology/pantoprazole/)
- [Esomeprazole](https://durgical.com/en/pharmacology/esomeprazole/)
- [Lansoprazole](https://durgical.com/en/pharmacology/lansoprazole/)
- [Omeprazole](https://durgical.com/en/pharmacology/omeprazole/)

## Related conditions

- [Gastro-oesophageal reflux disease (GERD)](https://durgical.com/en/conditions/gastro-oesophageal-reflux-disease/)
- [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/)
- [Helicobacter pylori gastritis](https://durgical.com/en/conditions/helicobacter-pylori-gastritis/)
- [Upper gastrointestinal bleeding](https://durgical.com/en/conditions/upper-gastrointestinal-bleeding/)

## Related

- [Na⁺/K⁺-ATPase (sodium pump)](https://durgical.com/en/biochemistry/enzymes/na-k-atpase/)
- [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/)

## 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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [ATP4A: Potassium-transporting ATPase alpha chain 1 (human)](https://rest.uniprot.org/uniprotkb/P20648.txt) (UniProt, 2026); [5YLU: Crystal structure of the gastric proton pump complexed with vonoprazan](https://www.rcsb.org/structure/5YLU) (RCSB Protein Data Bank, 2026); [OMEPRAZOLE capsule, delayed release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=516170d4-4913-4577-a2d2-f5c52d1e79c6) (DailyMed, US National Library of Medicine, 2026); [Omeprazole: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a693050.html) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/h-k-atpase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/h-k-atpase/