Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...

Bile is a crucial bodily fluid, characterized by its yellow-green color and alkaline nature. Produced in the liver, it is transported through the common hepatic duct into either the cystic duct, leading to the gallbladder, or directly into the common bile duct. The flow of bile is regulated by the sphincter of Oddi located at the entrance of the duodenum. When this sphincter is closed, bile is redirected to the gallbladder for storage and concentration.
Bile is released when dietary fats enter...

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...

Dietary triglycerides from chyme in the duodenum are mixed with bile salts produced by the liver to emulsify fats. As a result, large droplets are broken down into smaller ones, increasing the surface area for enzymatic action. Once emulsified, pancreatic lipases hydrolyze the triglycerides into free fatty acids and monoglycerides.
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...