Proton, potassium-ATPase

Im WB, Blakeman DP, Mendlein J, Sachs G (1984) Inhibition of proton potassium ATPase and proton accumulation in hog gastric membranes by trifluoperaz, verapamil and 8 N,N-diethylaminooctyl-3,4-5-trimethoxybenzoate. Biochim Biophys Acta 770 65-75... 

Crawson M A, Shull GE (1992) Isolation and characterization of a cDNA encoding the putative distal colonic proton potassium ATPase similarity of deduced animo acid sequence to proton potassium ATPase and sodium potassium ATPase and mRNA expression in distal colon and uterus. JBiol Chem 267 13740-13748... 

Wallmark B, Brandstrom A, Larsson H (1984) Evidence for acid-induced transformation of omeprazole into an active inhibitor of proton potassium ATPase within the parietal cell. Biochim Biophys Acta 778 549-558... 

Carrier-mediated transport involves cotransport of the absorbable species with a proton. The required proton gradient is hypothesized to be maintained by a Na+-H+ exchanger. The lumen of the intestine is acidic relative to the epithelial cell cytosol. The low cytosolic sodium concentration, required to produce the transporter driving force, is maintained by the Na K ATPase in the basolateral membrane. The sodium/proton exchanger working in concert with the sodium/potassium ATPase, therefore, results in a transport mechanism for the uptake of di- and tripeptides into the intestinal wall (Ganapthy and Leibach, 1985). 

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This class of enzymes [EC 3.6.1.36] (also known as the hydrogen/potassium-exchanging ATPase, the potassium-transporting ATPase, proton pump, and the gastric H+/K+ ATPase) catalyzes the hydrolysis of ATP to ADP and orthophosphate, coupled with the exchange of and ions. The gastric mucosal enzyme has been the best characterized. 

The uptake of potassium by microorganisms has been well studied. In the case of E. coli, kinetic investigations on different strains have demonstrated the presence of three or four transport systems. The presence of inducible pathways with widely different Km values for binding K+ allows the cell to accumulate K+ to a constant level under different environments. These transport pathways include those linked to the proton circuit and an example linked to a pump and ATP hydrolysis. Thus the Kdp system is a high affinity pathway with Km = 1 mol dm-3, and involves three proteins in the inner membrane of E. coli, including a K+-stimulated membrane ATPase. The KHA (i.e. K+-H+ antiport) path is driven by proton motive force, while the low affinity system TrKA depends on both ATP and the proton motive force.80,81,82 S. cerevisiae accumulates K+ by K+/H+ exchange.83 Potassium transport may thus be used to control intracellular pH. 

The final step of acid secretion is mediated by H /K -ATPase (E.C. 3.6.1.3.), the so-called gastric proton pump. Shull and Lindgrel reported that this enzyme consists of 1,033 amino acids with a combined molecular weight of 114,012 [9]. It shows about 62% homology of the amino acid sequence of NaVK -ATPase. Both enzymes are phosphorylated by ATP and potassium binding causes dephosphorylation and a conformational change in the protein. In contrast to Na /K -ATPase, which is widely distributed in all mammalian cells, HVK -ATPase is predominantly located at the apical membrane of the parietal cell, although a similar enzyme has... 

The apical membrane of the parietal cell forms, under nonsecretory conditions, tubulovesicular structures and, under secretory conditions, secretory cannaliculi. Its morphology depends on the secretory state of the parietal cell [14]. The lumen of the cannaliculi belongs to the extracellular compartment under secretory conditions Figure 4.1) and contains hydrochloric acid with a pH of about 1. H /K -ATPase exchanges protons for potassium ions across the apical surface. Thereby, the enzyme pumps out the protons against a proton gradient of 1 1,000,000. 

A potassium chloride co-transporter must be closely related to the H /K -ATPase during proton secretion. Potassium and chloride ions move across the apical membrane together with secreted protons Figure 4.1) [15-17]. Potassiiun is recycled while hydrochloric acid of the gastric juice is formed by chloride ions together with the secreted protons. Stimulation of gastric acid secretion across the apical membrane may predominantly reflect the activation or insertion of an active potassium chloride co-transporter rather than direct activation of HVK -ATPase [1]. 

Hydrochloric acid is secreted by parietal cells via H, K -ATPase pumps (proton pumps), of which there are more than one million per cell. The H, K -ATPase pumps utilize the phosphorylation of ATP to exchange water-solvated protons (protonated water, hydroxonium ion, H30 ) for potassium ions. In conjunction with parallel potassium and chloride ion conductances, this ATPase is responsible for the secretion of hydrochloric acid into the secretory canaliculus of the parietal cell, the enclosed space reaching a pH of near 1.0 (Rabon Reuben 1990). In the resting parietal cell, these pumps reside within the membranes of vesicles in the cell cytoplasm. When activated by histamine and gastrin, the parietal cells alter their shape and the vesicles merge with the outer cell membrane to form secretory canaliculi. 

Hie final step in acid secretion in the parietal cell is the extrusion ( pumping") of prottms. The membrane pump, an H /K -ATPase. catalyzes the exchange of hydrogen ions for potassium ions. Inhibition of this proton pump acts beyond the site of action of second messengers (e.g.. Ca and cAMP) and is independent of the action of secretogogues histamine, gastrin, and acetylcholine. Thus, acid pump inhibitors block basal and stimulated secretion. 

The last mediator of gastric secretion in the parietal cell is an H+,K+-ATPase (proton or acid pump) which is a member of the phosphorylating class of ion transport ATPases. Hydrolysis of ATP results in ion transport. This chemical reaction induces a conformational change in the protein that allows an electroneutral exchange of cytoplasmic H+ for K+. The pump is activated when associated with a potassium chloride pathway in the canalicular membrane which allows potassium chloride efflux into the extracytoplasmic space, and thus results in secretion of hydrochloric acid at the expense of ATP breakdown. The activity of the pump is determined by the access of K+ on this surface on the pump. In the absence of K+, the cycle stops at the level of the phosphoenzyme [137]. 

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