The proton pump (also called hydrogen-potassium adenosine triphosphatase) is an enzyme that plays an important role in the secretion of hydrochloric acid in the stomach. The proton pump consists of two subunits: the catalytic ?-subunit containing of 1033 amino acid residues and glycosylated ?-subunit containing 291 amino acid residues, as well as carbohydrate cytoplasmic fragments.
The proton pump (H+/K+ -ATPase) is present in large quantities in the parietal cells of the gastric mucosa. It transports the hydrogen ion H+ from the cytoplasm to the stomach through the apical membrane of the lining cells in exchange for the potassium ion K+ that the cytoplasm brings inside the cell. In this case, both cations are transported against the electrochemical gradient, and the hydrolysis of the ATP molecule serves as a source of energy for this transport. Simultaneously with protons of hydrogen, chlorine anions Cl- are entering the stomach lumen against the electrochemical gradient. K+ ions entering the cell leave the cell down the concentration gradient along with Cl- ions. H+ ions are formed in equivalent amounts with HCO3- with the dissociation of carbonic acid H2CO3 with the participation of carbonic anhydrase. HCO3 ions passively move into the blood down the concentration gradient through the basolateral membrane in exchange for Cl- ion. Thus, hydrochloric acid in the form of H+ and Cl- ions is released into the stomach lumen through the proton pump, whereas K+ ions entering back the lining cells.
The action of proton pump inhibitors (PPI) is based on the blocking of the proton pump, and these drugs are the most effective antiulcer medications. Once absorbed in the small intestine and got through the bloodstream into the gastric mucosa, PPIs accumulate in the secretory tubules of the lining cells. Here PPIs (at acidic pH) are activated and through the acid-dependent transformation are transformed into tetracyclic sulfenamide, which is covalently incorporated into the main cysteine groups of the proton pump. This prevents conformational transition of the proton pump and, thus blocks the production of hydrochloric acid by parietal cells of the stomach.

All proton pump inhibitors (omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole) are benzimidazole derivatives and have a very similar to its chemical structure. They differ in the structure of the radicals on the pyridine and benzimidazole rings.

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Since PPIs reduce the production of acid in the stomach by blocking an enzyme H+/K+ ATPase, they are commonly used to treat patients with conditions caused by either an overproduction of acid or exacerbated by stomach acid: acid reflux (GERD), Zollinger-Ellison syndrome (overproduction of acid), ulcers caused by NSAIDs, erosive esophagitis, together with antibiotics to treat eradication of H. pylori.

PPIs are used wisely to treat numerous conditions and they are generally well tolerated, however long-term use of PPIs has been linked to a number of safety concerns such as hypomagnesemia, vitamin B12 and iron deficiencies, osteoporosis, kidney disease, and even fractures (2).