ATPase gastric

Like Na,K-ATPase, gastric H,K-ATPase also exhibits a p-nitrophenylphosphatase (/>NPPase) activity. This phosphatase activity is dependent on Mg and K, or one of its congeners with the same order of selectivity as for the ATPase activity, yielding a specific activity of 6D84% of the maximal ATPase activity [4,136,137]. Phosphorylation by pNPP has not been demonstrated and transport is also not catalyzed by this substrate. As in the ATPase reaction the effect of on the... 

Parallel Operation of K+/H+ exchange and (X/HCO3 cotransport Amphiuma red cells, frog skin, cornea K+/H+ ATPase gastric epithelium... 

H+/K+-ATPase (gastric proton pump) inhibit gastric acid secretion, irrespective of the kind of stimulation. 

Anion-sensitive ATPase gastric mucosa 610 gmin-fraction... 

For control of gastric acid secretion, the H2 antagonists have encountered competition from the potent -ATPase inhibitors such as... 

FIGURE 10.13 Some of the sequence homologies in the nucleotide binding and phosphorylation domains of Na, K -ATPase, Ca -ATPase, and gastric H, K -ATPase. (Adapted from j0rgensm, P. L., and Andersen, J. R, 1988. Structnral basis for Ei - E2 confoyinational transitions in Na, K -pnmp and Cc -pnmp proteins. Journal of Membrane Biology 103 95-120)... 

FIGURE 10.16 The H+,lO-ATPase of gastric mucosal cells mediates proton transport into the stomach. Potassimn ions are recycled by means of an associated K /Cl cotransport system. The action of these two pnmps results in net transport of and Cl into the stomach. 

The discovery of the antiulcer activity of H2 antihistamine antagonists has revolutionized the treatment of that disease. A benzimidazole. Omeprazole (55), inhibits gastric secretion and subsequent ulcer formation by a quite different mechanism. Studies at the molecular level suggest that this compound inhibits K /H dependent ATPase and consequently shuts down the proton pumping action of this enzyme system. 

Tlie Na+/K+-ATPase belongs to the P-type ATPases, a family of more than 50 enzymes that also includes the Ca2+-ATPase of the sarcoplasmic reticulum or the gastric H+/K+-ATPase. P-Type ATPases have in common that during ion transport an aspartyl phos-phointermediate is formed by transfer of the y-phosphate group of ATP to the highly conserved sequence DKTGS/T [1]. 

Gastric H,K-ATPase inhibitors Potassium competitive acid blockers... 

The proton pump is the gastric H,K-ATPase, which secretes hydronium ions, H30+, in exchange forK+ into the secretory canaliculus generating a pH of <1.0 in... 

Proton Pump Inhibitors and Acid Pump Antagonists. Figure 2 Chemical mechanism of irreversible PPIs. PPIs are accumulated in acidic lumen and converted to active sulfenic acid and/or sulfenamide by acid catalysis. These active forms bind to extracytoplasmic cysteines of the gastric H.K-ATPase [3]. 

Fellenius E, Berglindh T, Sachs Getal(1981) Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature 290 159-161... 

Shin JM, Cho YM, Sachs G (2004) Chemistry of covalent inhibition of the gastric (H+,K+)-ATPase by proton pump inhibitors. J Am Chem Soc 126 7800-7811... 

Shin JM, S achs G (2004) Differences in binding properties of two proton pump inhibitors on the gastric H+,K+-ATPase in vivo. Biochem Pharmacol 68 2117-2127... 

ATC A02BC02 A02BD04 Use antisecretory, gastric HYK -ATPase inhibitor... 

In this chapter we will review the recent investigations of the structure of both the a and P subunit, and the function of gastric H,K-ATPase. We will proceed from a brief overview of the tissue distribution to a successive discussion of structure, kinetics, transport properties, lipid dependency, solubilization and reconstitution, and inhibitors of H,K-ATPase that may label functionally important domains of the enzyme. 

Until recently, the possibility that H,K-ATPase consists not only of a catalytic a subunit but also of other subunits was not examined. This was mainly due to the fact that SDS-PAGE of purified gastric H,K-ATPase preparations principally gave one protein band with an apparent molecular mass of about 100 kDa, which was reported to comprise 75% or more of the total amount of protein [6,66,67]. This mass is lower than the mass deduced from its cloned cDNA [40], but may be due to the higher electrophoretic mobility of membrane-bound proteins, as consequence of having relatively high contents of hydrophobic amino acid residues [68]. 

Hall et al. [62] identified in a separate study the same glycoprotein in H,K-ATPase vesicles isolated from porcine gastric mucosa. A stoichiometric ratio of 1.2 1.0 was found for the deglycosylated protein (35 kDa)/catalytic 94-kDa protein. Furthermore, compelling evidence that this glycoprotein is the H,K-ATPase p subunit was provided by N-terminal sequence analysis of three protease V8-obtained peptides of the 35-kDa core protein. These peptides showed 30% and 45% homology with the Na,K-ATPase pi and pi subunit, respectively. 

Gastric H,K-ATPase catalyses the 1 1 exchange of H for K upon hydrolysis of ATP, which results in vivo in a pH difference of more than six between the cytoplasm and the lumen [4-6]. Several reaction schemes have been developed to account for the hydrolysis of ATP and the transport of H and K" [14,104-107]. The basis for all these schemes is the Albers-Post scheme originally postulated for the mechanism of action of Na,K-ATPase [108,109]. 

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