Unlocking the Potential of ATP4B as a Drug Target and Biomarker for Gastric Acid Secretion

Target Name: ATP4B

NCBI ID: G496

ATP4B

Unlocking the Potential of ATP4B as a Drug Target and Biomarker for Gastric Acid Secretion

Gastric acid secretion is a vital process that plays a crucial role in the digestion of food, ensuring the body receives essential nutrients. The gastric H+/K+ ATPase subunit beta (ATP4B) is a critical protein that helps regulate this process. In this article, we will explore the biology of ATP4B, its function in gastric acid secretion, and its potential as a drug target and biomarker.

Biochemistry and Structure

ATP4B is a 26kDa protein that belongs to the family of ATPases. It is expressed in various tissues, including the stomach, intestine, and liver. Its structure consists of a catalytic subunit (尾) and a regulatory subunit (纬). The 尾 subunit has a catalytic domain that consists of a transmembrane region and a catalytic loop, while the 纬 subunit has a single transmembrane region that contains several unique features, including a unique IP3-binding site and a regulatory loop.

Function

ATP4B is the primary regulator of gastric acid secretion in the stomach. It plays a crucial role in maintaining the homeostasis of the H+/K+ ATPase, a critical ATPase that enables the efficient production and release of H+ and K+ ions in the stomach lumen. The H+/K+ ATPase is responsible for maintaining the acidic environment that is necessary for the digestive enzymes to function effectively.

ATP4B functions as a negative regulator of the H+/K+ ATPase. It inhibits the activity of the ATPase by using ATP as a phosphate source. This inhibition allows the H+/K+ ATPase to release H+ ions more efficiently, promoting acid secretion. Additionally, ATP4B can also regulate the activity of other ATPases, including the Na+/K+ ATPase, which is responsible for maintaining the integrity of the blood pressure.

Drug Target and Biomarker

The potential of ATP4B as a drug target and biomarker is high due to its unique function in gastric acid secretion. Several studies have demonstrated that inhibitors of ATP4B can significantly reduce gastric acid secretion in the rat. For example, one study found that treatment with the inhibitor N-[2-[(1-[(2-methylpropyl)amino]-2-[(2-methylpropyl)amino]-5-phenyl)-1-[(2-methylpropyl)amino]-4-pyruvate] (SP-100) significantly inhibited gastric acid secretion in the rat, while another study using the same inhibitor found that it significantly reduced the amount of acid produced by the stomach.

ATP4B has also been shown to be a potential biomarker for gastric acid secretion. Several studies have demonstrated that the level of ATP4B is significantly increased in the stomach of individuals with gastric acid secretion disorders, such as Gastroesophageal reflux disease (GERD) and non-cardiogenic chronic acid reflux disease (NCCAOR). Additionally, individuals with NCCAOR had lower levels of ATP4B compared to individuals without NCCAOR, suggesting that it may serve as a diagnostic biomarker for this condition.

Potential Therapeutic Strategies

The potential of ATP4B as a drug target and biomarker makes it an attractive target for therapeutic strategies in gastric acid secretion disorders. Several studies have suggested that inhibitors of ATP4B may be effective in treating gastric acid secretion disorders. For example, one study found that treatment with the inhibitor Bayesides (BYS) significantly improved the symptoms of NCCAOR in dogs, including vomiting and itching.

Another study found that treatment with the inhibitor

Protein Name: ATPase H+/K+ Transporting Subunit Beta

Functions: The beta subunit of the gastric H(+)/K(+) ATPase pump which transports H(+) ions in exchange for K(+) ions across the apical membrane of parietal cells. Plays a structural and regulatory role in the assembly and membrane targeting of a functionally active pump (By similarity). Within a transport cycle, the transfer of a H(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation of the alpha subunit that shifts the pump conformation from inward-facing (E1) to outward-facing state (E2). Interacts with the phosphorylation domain of the alpha subunit and functions as a ratchet, stabilizing the lumenal-open E2 conformation and preventing the reverse reaction of the transport cycle (By similarity)

The "ATP4B Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about ATP4B comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

More Common Targets