ABC-type bile acid transporter activity

Definition

Target type: molecularfunction

Enables the transfer of a solute or solutes from one side of a membrane to the other according to the reaction: bile acid(in) + ATP + H2O -> bile acid(out) + ADP + phosphate. [RHEA:50048]

ABC-type bile acid transporters are membrane proteins that play a crucial role in the transport of bile acids across cell membranes. Bile acids are synthesized in the liver from cholesterol and are essential for the digestion and absorption of fats. They are amphipathic molecules, meaning they have both hydrophilic (water-loving) and hydrophobic (water-fearing) regions. This allows them to interact with both water and fats, enabling them to emulsify fats in the gut and facilitate their digestion.

ABC-type bile acid transporters belong to the ATP-binding cassette (ABC) superfamily of transmembrane proteins. These transporters utilize the energy derived from ATP hydrolysis to actively transport substrates across cell membranes against their concentration gradient. This active transport mechanism is essential for maintaining the appropriate concentrations of bile acids in different tissues and organs.

There are two major types of ABC-type bile acid transporters:

* **Bile salt export pump (BSEP):** BSEP is located in the canalicular membrane of hepatocytes, the liver cells. It is responsible for the efflux of bile acids from the liver into the bile canaliculi, which eventually drain into the gallbladder. BSEP plays a critical role in the detoxification of bile acids and the regulation of bile acid homeostasis.
* **Organic solute transporter alpha (OSTα):** OSTα is located in the basolateral membrane of ileal enterocytes, the cells lining the small intestine. It facilitates the reabsorption of bile acids from the intestinal lumen back into the bloodstream. This reabsorption process is important for conserving bile acids and ensuring that they are available for subsequent rounds of digestion.

The molecular function of ABC-type bile acid transporters involves several steps:

1. **Binding of bile acids:** Bile acids bind to specific sites on the transporter protein. These binding sites have a high affinity for bile acids, ensuring efficient transport.
2. **Conformational change:** Binding of bile acids triggers a conformational change in the transporter protein, opening a channel across the cell membrane.
3. **Transport of bile acids:** The bile acids are then transported across the membrane through the open channel.
4. **ATP hydrolysis:** ATP hydrolysis provides the energy necessary for the transport process.
5. **Conformational reset:** After the transport cycle is complete, the transporter protein returns to its original conformation, ready for another round of transport.

Mutations in genes encoding ABC-type bile acid transporters can lead to various diseases, including:

* **Progressive familial intrahepatic cholestasis (PFIC):** PFIC is a genetic disorder characterized by impaired bile acid transport, leading to liver damage and cirrhosis. Mutations in BSEP are the most common cause of PFIC.
* **Intrahepatic cholestasis of pregnancy (ICP):** ICP is a liver disorder that occurs during pregnancy and is characterized by elevated bile acid levels in the blood. Mutations in BSEP have been implicated in some cases of ICP.
* **Alagille syndrome:** Alagille syndrome is a rare genetic disorder affecting multiple organs, including the liver. Mutations in the JAG1 gene, which is involved in the regulation of BSEP expression, can cause Alagille syndrome.

In summary, ABC-type bile acid transporters play a crucial role in the transport of bile acids across cell membranes, ensuring proper bile acid homeostasis and facilitating the digestion and absorption of fats. Their activity is essential for maintaining liver health and overall metabolic function.'
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Proteins (6)

Compounds (973)