User:Alisha, Deepa, Pamiz/Sandbox 1
From Proteopedia
Introduction
Esomeprazole is a Proton Pump Inhibitor (PPI) that binds to H+/K+-ATPase and inhibits the secretion of gastric acid from the parietal cells into the lumen of the stomach. Esomeprazole’s commercial brand name, Nexium, is used to treat Gastro-esophageal Reflux Disease (GERD), peptic and gastric ulcers, and Zollinger-Ellison syndrome. Ulcers caused by the bacterium Helicobacter pylori can be treated using Esomeprazole in conjunction with proper antibiotics.1 These result in gastric acid accumulation into the lumen of the stomach from the parietal cells.2 Gastric acid is released through the H+/K+-ATPase pump, which is the final step in acid release.2 Esomeprazole is an irreversible inhibitor of the pump.2
H+/K+-ATPase
The H+/K+-ATPase pump is located within the cytoplasmic membrane of resting parietal cells (Figure 1); when activated, the ATPase is translocated to the canalicular membrane and begins to pump cytoplasmic H+ into the canalicular space, in exchange for extracellular K+ ions. The H+/K+-ATPase pump regulates the final step in the acid secretion pathway.3 Targeting this enzyme using PPIs is the most effective therapeutic control agent of gastric acid secretion.3 Image:Canalicular Membrane.jpgFigure 1. Cartoon representation of gastric parietal cells, mucus cells, Canaliculi, and the direction of H+ secretion into the lumen of the stomach. Figure created using Microsoft Word 2010. H+/K+-ATPase is part of the P-type ATPase enzyme family, and transports cations across the membrane.5 The pump goes against the H+ concentration gradient found in the stomach and is powered through ATP hydrolysis.5 The inorganic Pi produced drives a conformational change in the enzyme and allows release of H+ into the highly acidic The H+/K+-ATPase pump, located within the cytoplasmic membrane of resting parietal cells, gets translocated upon activation to the canalicular membrane and pumps cytoplasmic H+ into the canalicular space, in exchange for extracellular K+ ions. It is a pro-drug that is protonated twice in the acidic environment of the parietal cell to form the active inhibitor, sulfenamide which forms disulfide bonds with Cys 813 and Cys 892 on the α subunit of the H+/K+-ATPase. Esomeprazole inhibits the final step in the secretion of gastric acid.
