Hydrogen potassium ATPase - AbsoluteAstronomy.com

Gastric hydrogen potassium ATPase is also known as H⁺/K⁺ ATPase

Function and location

The gastric hydrogen potassium ATPase

ATPase

ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

or H⁺/K⁺ ATPase is the proton pump

Proton pump

A proton pump is an integral membrane protein that is capable of moving protons across a cell membrane, mitochondrion, or other organelle. Mechanisms are based on conformational changes of the protein structure or on the Q cycle.-Function:...

of the stomach

Stomach

The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...

and, as such, is the enzyme primarily responsible for the acidification of the stomach contents (see gastric acid

Gastric acid

Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride...

). The H⁺/K⁺ ATPase is found in parietal cells, which are highly specialised epithelial cells located in the inner cell lining of the stomach called the gastric mucosa. Parietal cells possess an extensive secretory membrane system and the H⁺/K⁺ ATPase is the major protein constituent of these membranes.

Genes and Protein structure

The H⁺/K⁺ ATPase is a heterodimeric protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

, the product of 2 genes. The gene ATP4A encodes the H⁺/K⁺ 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⁺/K⁺ 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⁺/K⁺ ATPase β subunit stabilizes the H⁺/K⁺ 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⁺/K⁺ ATPase α subunit.

Enzyme activity of the H⁺/K⁺ 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⁺/K⁺ ATPase transports one hydrogen ion (H⁺) from the cytoplasm of the parietal cell in exchange for one potassium ion (K⁺) retrieved from the gastric lumen. As an ion pump the H⁺/K⁺ 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 from adenosine triphosphate

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

(ATP) to the H⁺/K⁺ ATPase during the transport cycle. This phosphate transfer powers a conformational change in the enzyme that helps drive ion transport.

Inhibition of H⁺/K⁺ ATPase

Inhibiting gastric acid secretion by blocking the activity is a very common clinical intervention used in diseases including dyspepsia, peptic ulcer

Peptic ulcer

A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...

disease, and gastroesophageal reflux disease

Gastroesophageal reflux disease

Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...

(GORD/GERD). Two drug categories are commonly used to inhibit H⁺/K⁺ ATPase activity. H₂-receptor antagonists

H2-receptor antagonist

The H2 receptor antagonists are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective ...

, like cimetidine

Cimetidine

Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...

(Tagamet), inhibit the signalling pathway that leads to activation of the ATPase. Proton pump inhibitor

Proton pump inhibitor

Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...

s (PPIs) , like omeprazole

Omeprazole

Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...

(Prilosec), directly bind to and inactivate the H⁺/K⁺ ATPase.

Function and location

Genes and Protein structure

Enzyme activity of the H+/K+ ATPase

Inhibition of H+/K+ ATPase

See also

Enzyme activity of the H⁺/K⁺ ATPase

Inhibition of H⁺/K⁺ ATPase