It's known that proton pumps exist in all cells in our bodies and help us to get rid of damaged proteins (present a disposal system).

PPIs (omeprazole, pantoprazole, esomeprazole, lansoprazole and other prazole) shut down this little pumps in our stomach, therefore we get a higher PH and the lining can eventually heal by time.

Do these drugs shut down all the pumps across our body or do they just target the ones inside the stomach?

Refer to third paragraph

2 Answers 2


"Proton pump" is a broad category of proteins rather than a specific pump.

The drugs called "proton pump inhibitors (PPIs)" to reduce stomach acid target a specific proton pump, the hydrogen/potassium ATPase.

Of course, it is possible for drugs to have off-target effects at other proteins, especially similar ones. It is also possible for side-effects of PPIs that are secondary to the reduction in gastric acid, which can affect digestion and absorption of certain nutrients.

Lysosomes and other organelles use a different proton pump, the V-ATPase. If you search for papers involving specific PPIs and the V-ATPase it does appear that V-ATPase can potentially be affected by PPIs, and this has been considered as an anti-tumor strategy by some:

Fais, S., De Milito, A., You, H., & Qin, W. (2007). Targeting vacuolar H+-ATPases as a new strategy against cancer. Cancer research, 67(22), 10627-10630.

I'm guessing the article you linked to is referring to this paper:

Yepuri, G., Sukhovershin, R., Nazari-Shafti, T. Z., Petrascheck, M., Ghebre, Y. T., & Cooke, J. P. (2016). Proton pump inhibitors accelerate endothelial senescence. Circulation research, 118(12), e36-e42.

In this paper, cultured endothelial cells are incubated with the PPI esomeprazole at 5 or 10 μmol/L. They found increased pH (reduced acidity) in intracellular comparments imaged with a pH-sensitive dye, and various symptoms of endothelial dysfunction after esomeprazole treatment.


First of all, if you found papers that suggest certain unexplored side effects, it means the research is underway and it can very well be that in the next years we get new information about how drugs work.

Now to the actual question. From the pharmacokinetic point of view, PPIs only affect proton pumps of the stomach. The solution behind this is very simple: PPIs are pro-drugs, that only get activated when surrounding pH is less than 1. Since the only place in the body where this is the case are canaliculi of the gastric glands, only here PPIs bind to their target proteins.

This compound [omeprazole] is a weak base ~pKa 4. The H+, K+-ATPase in the parietal cell secretes acid into the secretory canaliculus generating a pH of < 1.0 in the lumen of this structure. The acidity of this space allows accumulation of weak bases of this pKa. Weak bases of a pKa less than 4.0 can be accumulated only in this acidic space and no other acidic space in the body. Then, this compound is rapidly activated by the high acidity and inhibits acid secretion by binding to the cysteines accessible to the activated form.

Source: Jai Moo Shin and Nayoung Kim. "Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors". J Neurogastroenterol Motil. 2013 Jan; 19(1): 25–35. doi:10.5056/jnm.2013.19.1.25

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