View source for Hydrogen potassium ATPase



==Overview==
{{protein
| Name = ATPase, H+/K+ exchanging, alpha polypeptide
| caption = 
| image = 
| width = 
| HGNCid = 819
| Symbol = ATP4A
| AltSymbols = 
| EntrezGene = 495
| OMIM = 137216
| RefSeq = NM_000704
| UniProt = P20648
| PDB = 
| ECnumber = 3.6.3.10
| Chromosome = 19
| Arm = q
| Band = 13.1
| LocusSupplementaryData = 
}}
{{protein
| Name = ATPase, H+/K+ exchanging, beta polypeptide
| caption = 
| image = 
| width = 
| HGNCid = 820
| Symbol = ATP4B
| AltSymbols = 
| EntrezGene = 496
| OMIM = 137217
| RefSeq = NM_000705
| UniProt = P51164
| PDB = 
| ECnumber = 3.6.3.10
| Chromosome = 13
| Arm = q
| Band = 34
| LocusSupplementaryData = 
}}
{{SI}}
Gastric '''hydrogen potassium ATPase''' is also known as '''H<sup>+</sup>/K<sup>+</sup> ATPase''' 

== Function and location ==
The gastric hydrogen potassium [[ATPase]] or H<sup>+</sup>/K<sup>+</sup> ATPase is the [[proton pump]] of the [[stomach]] and as such is the enzyme primarily responsible for the acidification of the stomach contents (see [[gastric acid]]). The H<sup>+</sup>/K<sup>+</sup> ATPase is found in [[parietal cells]] which are highly specialised [[epithelial]] cells located in the inner cell lining of the stomach, which is called the gastric [[mucosa]]. Parietal cells possess an extensive secretory membrane system and the H<sup>+</sup>/K<sup>+</sup> ATPase is the major protein constituent of these membranes.

== Genes and Protein structure ==
The H<sup>+</sup>/K<sup>+</sup> ATPase is a heterodimeric [[protein]], the product of 2 genes. The gene ''ATP4A'' encodes the H<sup>+</sup>/K<sup>+</sup> ATPase  α subunit contains and is an ~ 1000 amino acid protein that contains the catalytic sites of the enzyme and forms the pore through the cell membrane that allows the transport of ions. The gene ''ATP4B'' encodes the β subunit of the H<sup>+</sup>/K<sup>+</sup> ATPase, which is an ~ 300 amino acid protein with a 36 amino acid N-terminal cytoplasmic domain, a single transmembrane domain, and a highly glycosylated extracellular domain. The H<sup>+</sup>/K<sup>+</sup> ATPase β subunit stabilizes the H<sup>+</sup>/K<sup>+</sup> ATPase α subunit and is required for function of the enzyme. It also appears to contain signals that direct the heterodimer to membrane destinations within the cell, although some of these signals are subordinate to signals found in H<sup>+</sup>/K<sup>+</sup> ATPase α subunit.

== Enzyme activity of the H<sup>+</sup>/K<sup>+</sup> ATPase ==
The H+/K+ ATPase is a member of the P-type ATPase superfamily, a large family of related proteins that transport ions, most usually cations, across biological membranes in nearly all species. The H<sup>+</sup>/K<sup>+</sup> ATPase transports one hydrogen ion (H<sup>+</sup>) from the cytoplasm of the parietal cell in exchange for one potassium ion (K<sup>+</sup>) retrieved from the gastric lumen. As an ion pump the H<sup>+</sup>/K<sup>+</sup> ATPase is able to transport ions against a concentration gradient using energy derived from the hydrolysis of ATP. Like all P-type ATPases a phosphate group is transferred form [[adenosine triphosphate]] (ATP) to the H<sup>+</sup>/K<sup>+</sup> ATPase during the transport cycle. This phosphate transfer powers a conformational change in the enzyme that helps drive ion transport.

== Inhibition of H<sup>+</sup>/K<sup>+</sup> ATPase ==
Inhibiting gastric acid secretion by blocking the activity is a very common clinical intervention used in diseases including dyspepsia, [[peptic ulcer]] disease and [[gastroesophageal reflux disease]] (GORD/GERD). Two drug categories are commonly used to inhibit H<sup>+</sup>/K<sup>+</sup> ATPase activity. [[H2-receptor antagonist|H<sub>2</sub>-receptor antagonists]] inhibit the signalling pathway that leads to activation of the ATPase. [[Proton pump inhibitor]]s (PPIs) directly bind to and inactivate the H<sup>+</sup>/K<sup>+</sup> ATPase.

== See also ==

* [[Gastric acid]]
* [[Parietal cell]]
* [[Stomach]]
* [[Proton pump inhibitor]]

==External links==
*Cell biology of acid secretion by the parietal cell. ''Annual Review of Physiology''. 2003; 65:103-31. [http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.physiol.65.072302.114200 link]
*Kuhlbrandt W (2004) [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15071553&query_hl=50&itool=pubmed_docsum Biology, structure and mechanism of P-type ATPases.] ''Nature Reviews. Molecular Cell Biology''. 2004; 5(4):282-95.  Accessed [[January 9]], [[2007]].
*Dunbar LA, Caplan MJ. (2001) [http://www.jbc.org/cgi/content/full/276/32/29617 Ion pumps in polarized cells: sorting and regulation of the H<sup>+</sup>/K<sup>+</sup>- and H<sup>+</sup>/K<sup>+</sup>-ATPases.] ''Journal of Biological Chemistry''. 276:29617-20. Accessed [[January 9]], [[2007]].
*Sachs G, Shin JM, Briving C, Wallmark B, Hersey S. (1995) [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7598495&query_hl=53&itool=pubmed_docsum The pharmacology of the gastric acid pump: the H<sup>+</sup>/K<sup>+</sup> ATPase.] ''Annual Review of Pharmacology and Toxicology''. 35:277-305. Accessed [[January 9]], [[2007]].
* {{MeshName|Potassium+Hydrogen+ATPase}}


{{ATPases}}
{{Ion pumps}}

[[Category:Body fluids]]
[[Category:Digestive system]]
[[Category:Hydrogen biology]]
[[Category:Transport proteins]]

[[de:Protonen-Kalium-Pumpe]]

{{WH}}
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